virus biology 1

virus
Introduction

an infectious agent of small size and simple composition that can multiply only in living cells of animals, plants, or bacteria. The name is from a Latin word meaning

“slimy liquid” or “poison.”

The earliest indications of the biological nature of viruses came from studies in 1892 by the Russian scientist Dmitry I. Ivanovsky and in 1898 by the Dutch scientist Martinus W. Beijerinck. Beijerinck first surmised that the virus under study was a new kind of infectious agent, which he designated contagium vivum fluidum, meaning that it was a live, reproducing organism that differed from other organisms. Both of these investigators found that a disease of tobacco plants could be transmitted by an agent, later called tobacco mosaic virus, passing through a minute filter that would not allow the passage of bacteria. This virus and those subsequently isolated would not grow on an artificial medium and were not visible under the light microscope. In independent studies in 1915 by the British investigator Frederick W. Twort and in 1917 by the French Canadian scientist Félix H. d'Hérelle, lesions in cultures of bacteria were discovered and attributed to an agent called bacteriophage (“eater of bacteria”), now known to be viruses that specifically infect bacteria.

The unique nature of these organisms meant that new methods and alternative models had to be developed to study and classify them. The study of viruses confined exclusively or largely to humans, however, posed the formidable problem of finding a susceptible animal host. In 1933 the British investigators Wilson Smith, Christopher H. Andrewes, and Patrick P. Laidlaw were able to transmit influenza to ferrets, and the influenza virus was subsequently adapted to mice. In 1941 the American scientist George K. Hirst found that influenza virus grown in tissues of the chicken embryo could be detected by its capacity to agglutinate (draw together) red blood cells.

A significant advance was made by the American scientists John Enders, Thomas Weller, and Frederick Robbins, who in 1949 developed the technique of culturing cells on glass surfaces; cells could then be infected with the viruses that cause polio (poliovirus) and other diseases. (Until this time, the poliovirus could be grown only in the brains of chimpanzees or the spinal cords of monkeys.) Culturing cells on glass surfaces opened the way for diseases caused by viruses to be identified by their effects on cells (cytopathogenic effect) and by the presence of antibodies to them in the blood. Cell culture then led to the development and production of vaccines.(preparations used to elicit immunity against a disease) such as the poliovirus vaccine.
Scientists were soon able to detect the number of bacterial viruses in a culture vessel by measuring their ability to break apart (lyse) adjoining bacteria in an area of bacteria (lawn) overlaid with an inert gelatinous substance called agar—viral action that resulted in a clearing, or “plaque.”

The American scientist Renato Dulbecco in

1952 applied this technique to measuring the number of animal viruses that could produce plaques in layers of adjoining animal cells overlaid with agar. In the 1940s the development of the electron microscope permitted individual virus particles to be seen for the first time, leading to the classification of viruses and giving insight into their structure.

Advancements that were made in chemistry, physics, and molecular biology since the 1960s have revolutionized the study of viruses. For example, electrophoresis on gel substrates gave a deeper understanding of the protein and nucleic acid composition of viruses. More-sophisticated immunologic procedures, including the use of monoclonal antibodies directed to specific antigenic sites on proteins, gave a better insight into the structure and function of viral proteins. The progress made in the physics of crystals that could be studied by X-ray diffraction provided the high resolution required to discover the basic structure of minute viruses. Applications of new knowledge about cell biology and biochemistry helped to determine how viruses use their host cells for synthesizing viral nucleic acids and proteins.
The revolution that took place in the field of molecular biology allowed the genetic information encoded in nucleic acids of viruses—which enables viruses to reproduce, synthesize unique proteins, and alter cellular functions—to be studied. In fact, the chemical and physical simplicity of viruses has made them an incisive experimental tool for probing the molecular events involved in certain life processes.
This article discusses the fundamental nature of viruses: what they are, how they cause infection, and how they may ultimately cause disease or bring about the death of their host cells. For more-detailed treatment of specific viral diseases, see infection.
 

General features
Definition

Viruses occupy a special taxonomic position: they are not plants, animals, or prokaryotic bacteria (single-cell organisms without defined nuclei), and they are generally placed in their own kingdom. In fact, viruses should not even be considered organisms, in the strictest sense, because they are not free-living; i.e., they cannot reproduce and carry on metabolic processes without a host cell.
All true viruses contain nucleic acid—either DNA (deoxyribonucleic acid) or RNA (ribonucleic acid)—and protein. The nucleic acid encodes the genetic information unique for each virus. The infective, extracellular (outside the cell) form of a virus is called the virion. It contains at least one unique protein synthesized by specific genes in the nucleic acid of that virus. In virtually all viruses, at least one of these proteins forms a shell (called a capsid) around the nucleic acid. Certain viruses also have other proteins internal to the capsid; some of these proteins act as enzymes, often during the synthesis of viral nucleic acids. Viroids (meaning “viruslike”) are disease-causing organisms that contain only nucleic acid and have no structural proteins. Other viruslike particles called prions are composed primarily of a protein tightly complexed with a small nucleic acid molecule. Prions are very resistant to inactivation and appear to cause degenerative brain disease in mammals, including humans.

Viruses are quintessential parasites; they depend on the host cell for almost all of their life-sustaining functions. Unlike true organisms, viruses cannot synthesize proteins, because they lack ribosomes (cell organelles) for the translation of viral messenger RNA (mRNA; a complementary copy of the nucleic acid of the nucleus that associates with ribosomes and directs protein synthesis) into proteins. Viruses must use the ribosomes of their host cells to translate viral mRNA into viral proteins.

Viruses are also energy parasites; unlike cells, they cannot generate or store energy in the form of adenosine triphosphate (ATP). The virus derives energy, as well as all other metabolic functions, from the host cell. The invading virus uses the nucleotides and amino acids of the host cell to synthesize its nucleic acids and proteins, respectively. Some viruses use the lipids and sugar chains of the host cell to form their membranes and glycoproteins (proteins linked to short polymers consisting of several sugars).

The true infectious part of any virus is its nucleic acid, either DNA or RNA, but never both. In many viruses, but not all, the nucleic acid alone, stripped of its capsid, can infect (transfect) cells, although considerably less efficiently than can the intact virions.

The virion capsid has three functions: (1) to protect the viral nucleic acid from digestion by certain enzymes (nucleases), (2) to furnish sites on its surface that recognize and attach (adsorb) the virion to receptors on the surface of the host cell, and, in some viruses, (3) to provide proteins that form part of a specialized component which enables the virion to penetrate through the cell surface membrane or, in special cases, to inject the infectious nucleic acid into the interior of the host cell.
 

Host range and distribution
 Soon...

Infectious Disease Questions

58.  Which of the following statements about the treatment of the above patient is correct?
a.  Oral antibiotic therapy is never appropriate
b.  Trimethoprim-sulfamethoxazole is the treatment of choice in the nonallergic
 patient
c.  Concomitant corticosteroids should always be avoided
d.  Tetracycline is more effective than erythromycin

59.  A 25-year-old male from East Tennessee had been ill for 5 days with fever, chills, and headache when he noted a rash that developed on his palms and soles. In addition to macular lesions, petechiae are noted on the wrists and ankles. The patient has spent the summer camping. The most important fact to be determined in the history is
a.  Exposure to contaminated springwater
b.  Exposure to raw pork
c.  Exposure to ticks
d.  Exposure to prostitutes

60.  A  19-year-old male has a history of athlete’s foot but is otherwise
healthy when he develops the sudden onset of fever and pain in the right
foot and leg. On physical exam, the foot and leg are fiery red with a well-
defined indurated margin that appears to be rapidly advancing. There is
tender inguinal lymphadenopathy. The most likely organism to cause this
infection is
a.  Staphylococcus epidermidis
b.  Tinea pedis
c.  Streptococcus pyogenes
d.  Mixed anaerobic infection

61.  An 18-year-old male has been seen in clinic for urethral discharge. He
is treated with ceftriaxone, but the discharge has not resolved and the cul-
ture has returned as no growth. The most likely etiologic agent to cause this
infection is
a.  Ceftriaxone-resistant gonococci
b.  Chlamydia psittaci
c.  Chlamydia trachomatis
d.  Herpes simplex

Items 62-68
Match the clinical description with the most likely etiologic agent.
a.  Candida albicans
b.  Aspergillus flavus
c.  Coccidioides immitis
d.  Herpes simplex type 1
e.  Herpes simplex type 2
f.  Hantavirus
g.  Tropheryma whippelii
h.  Coxsackievirus B
i.  Histoplasma capsulatum
j.  Human parvovirus
k.  Cryptococcus neoformans

62.  An HIV-positive patient develops fever and dysphagia; endoscopic biopsy shows yeast and hyphae. (CHOOSE 1 AGENT)
63.  A 50-year-old develops sudden onset of bizarre behavior. CSF shows 80 lymphocytes; magnetic resonance imaging shows temporal lobe abnormalities. (CHOOSE 1 AGENT)
64.  A patient with a previous history of tuberculosis now complains of hemoptysis. There is an upper lobe mass with a cavity and a crescentshaped air-fluid level. (CHOOSE 1 AGENT)
65.  A Filipino patient develops a pulmonary nodule after travel through the American Southwest. (CHOOSE 1 AGENT)
66.  A 35-year-old male who had a fever, cough, and sore throat develops
chest pain after several days with diffuse ST segment elevations on ECG.
(CHOOSE 1 AGENT)

67.  Overwhelming pneumonia with adult respiratory distress syndrome occurs on an Indian reservation in the Southwest following exposure to deer mice. (CHOOSE 1 AGENT)
68.  A child develops an erythematous rash appearing as a slapped cheek. (CHOOSE 1 AGENT)

5-7.  The answers are 5-c, 6-b, 7-a. (Braunwald, 15/e, pp 1073-1074.)
This young woman presents with symptoms of both upper and lower res-
piratory infection. The combination of sore throat, bullous myringitis, and
infiltrates on chest x-ray is consistent with infection due to M. pneumoniae.
This minute organism is not seen on Gram stain. Neither S. pneumoniae nor
H. influenzae would produce this combination of upper and lower respira-
tory tract symptoms. The patient is likely to have high titers of IgM cold
agglutinins. The low hematocrit and elevated reticulocyte count reflect a
hemolytic anemia that can occur from mycoplasma infection. These IgM-
class antibodies are directed to the I antigen on the erythrocyte membrane.
The treatment of choice for mycoplasma infection is erythromycin.

8-10.  The answers are 8-c, 9-a, 10-c. (Braunwald, 15/e, pp 1109-1111.)
This young man presents with classic signs and symptoms of infectious
mononucleosis. In a young patient with fever, pharyngitis, lymphadenopa-
thy, and lymphocytosis, the peripheral blood smear should be evaluated for
atypical lymphocytes. A heterophile antibody test should be performed.
The symptoms described in association with atypical lymphocytes and a
positive heterophile test are virtually always due to Epstein-Barr virus. Nei-
ther liver biopsy nor lymph node biopsy is necessary. Workup for toxo-
plasmosis or cytomegalovirus infection or hepatitis B and C would be
considered in heterophile-negative patients, Hepatitis does not occur in the
setting of rheumatic fever, and an antistreptolysin O titer is not indicated.
Corticosteroids are indicated in the treatment of infectious mononucleosis
when severe hemolytic anemia is demonstrated or when airway obstruc-
tion occurs. Neither fatigue nor the complication of hepatitis is an indica-
tion for corticosteroid therapy.

11-14. The answers are 11-c, 12-d, 13-e, 14-a. (Braunwald, 15/e, pp
809-814, 882-885, 959, 1009, 1620.) The 30-year-old-female with mitral
valve prolapse has developed subacute bacterial endocarditis. The likely eti-
ologic agent is a viridans streptococci. Viridans streptococci cause most
cases of subacute bacterial endocarditis. No other agent listed is likely to
cause this infection. The 80-year-old-male with a Foley catheter in place has
developed a nosocomial infection likely secondary to urosepsis. Providencia
species frequently cause urinary tract infection in the hospitalized patient.
The young man with a fluctuant lesion and fistula over the mandible pre-
sents a classic picture of cervicofacial actinomycosis. The sickle cell anemia

 

Infectious disease Answers 2

25. The answer is b. (Braunwald, 15/e, pp 1125-1131.) Influenza A is a potentially lethal disease in the elderly and chronically debilitated patient. In institutional settings such as nursing homes, outbreaks are likely to be particularly severe. Thus prophylaxis is extremely important in this setting. All residents should receive the vaccine unless they have known egg allergy (patients can choose to decline the vaccine). Since protective antibodies to the vaccine will not develop for 2 weeks, amantadine can be used for protection against influenza A during the interim 2-week period. A reduced dose is given to elderly patients. 26. The answer is c. (Braunwald, 15/e, p 896.) In the treatment of hospitalacquired staphylococcal pneumonia, the incidence of methicillin-resistant staph in the local facility will be very important. In most hospitals, methicillin-resistant staph is common enough to require initial therapy with vancomycin. Oxacillin would be the drug of choice only if the incidence of methicillin-resistant staph is very low. Quinolones are often useful in the treatment of community-acquired pneumonia, but they would not be effective against methicillin-resistant staph. 27. The answer is b. (Braunwald, 15/e, p 1479.) The Infectious Disease Society of America’s guidelines on the treatment of community-acquired pneumonia still recommend the use of sputum gram stain and culture. This is particularly important in the era of multi-antibiotic-resistant S. pneumoniae. Sputum culture and sensitivity can direct specific antibiotic therapy for the patient as well as provide epidemiologic information for the community as a whole. A good sputum sample showing many polymorphonuclear leuko- cytes and few squamous epithelial cells can give important clues to etiology. A Gram stain that shows gram-positive lancet-shaped diplococci intracellu- larly is good evidence for pneumococcal infection. Empirical antibiotic ther- apy becomes more difficult in community-acquired pneumonia as more pathogens are recognized and as the pneumococcus develops resistance to penicillin, macrolides, and even quinolones. 28. The answer is b. (Braunwald, 15/e, pp 1031-1034.) Multidrugresistant tuberculosis (TB) has become an increasing problem in several settings, including correctional facilities and health care institutions. Noncompliance or poor compliance with prescribed anti-TB medications is the major factor in the development of multiple drug resistance. When the disease is suspected, patients should be placed in respiratory isolation and sputum should be obtained for AFB stain, culture, and sensitivity. Treatment of high-risk patients, such as this patient, should be supervised, and multidrug resistance should be assumed. Regular screening of inmates and staff for TB is important for preventing the spread of TB within the facility and for early diagnosis of new infections. 29. The answer is b. (Braunwald, 15/e, pp 242, 954.) The outbreak described is similar to those previously attributed to Escherichia coli 0157:H7. Ingestion of and infection with this organism may result in a spectrum of illnesses, including mild diarrhea, hemorrhagic colitis with bloody diarrhea, acute renal failure, and death. Infection has been associated with ingestion of contaminated beef (in particular ground beef ), ingestion of raw milk, and contamination via the fecal-oral route. Cooking ground beef so that it is no longer pink is an effective means of preventing infection, as are hand washing and pasteurization of milk. 30. The answer is b. (Stobo, 23/e, pp 547-551.) Patients may develop fever as a result of infectious or noninfectious diseases. The term fever of unknown origin (FUO) is applied when significant fever persists without a known cause after an adequate evaluation. Several studies have found the leading causes of FUO to include infections, malignancies, collagen vascu- lar diseases, and granulomatous diseases. As the ability to more rapidly diagnose some of these diseases increases, their likelihood of causing undi- agnosed persistent fever lessens. Infections such as intraabdominal abscesses, tuberculosis, hepatobiliary disease, endocarditis (especially if the patient had previously taken antibiotics), and osteomyelitis may cause FUO. In immunocompromised patients, such as those infected with HIV, a number of opportunistic infections or lymphomas may cause fever and escape early diagnosis. Self-limited infections such as influenza should not cause fever that persists for many weeks. Neoplastic diseases such as lymphomas and some solid tumors (e.g., hypernephroma and primary or metastatic disease of the liver) are associated with FUO. A number of col- lagen vascular diseases may cause FUO. Since conditions such as systemic lupus erythematosus are more easily diagnosed today, they are less frequent causes of this syndrome. Adult Still’s disease, however, is often difficult to diagnose. Other causes of FUO include granulomatous diseases (i.e., giant cell arteritis, regional enteritis, sarcoidosis, and granulomatous hepatitis), drug fever, and peripheral pulmonary emboli. Factitious fever is most com- mon among young adults employed in health-related positions. A prior psychiatric history or multiple hospitalizations at other institutions may be clues to this condition. Such patients may induce infections by self- injection of nonsterile material, with resultant multiple abscesses or polymicrobial infections. Alternatively, some patients may manipulate their thermometers. In these cases, a discrepancy between temperature and pulse or between oral temperature and witnessed rectal temperature will be observed. 31. The answer is a. (Mandell, 5/e, pp 917-923.) Although no evidence exists that prophylactic antibiotic therapy prevents endocarditis, prophy- laxis is recommended for all procedures that may generate bacteremias. Following cardiac catheterization, blood cultures obtained from a distal vein are rarely positive. Thus, prophylactic antibiotics are not currently recommended for cardiac catheterization. Bacteremia commonly occurs following other procedures such as periodontal surgery, tonsillectomy, and prostate surgery. 32. The answer is d. (Mandell, 5/e, pp 1811-1819.) Rabies is caused by a bullet-shaped rhabdovirus. In the United States, dogs are seldom rabid. The animals that present the most danger are wild skunks and bats; foxes are also possible carriers. Raccoons are responsible for an increasing num- ber of cases in the mid-Atlantic states. The incubation period ranges from 4 days to many years, but is usually between 20 and 90 days. The incuba- tion period is usually shorter with a bite to the head than with one to an extremity. In humans, only four definite recoveries from established infec- tion have been reported. Nonimmunized animals that have been bitten should be killed and their brains submitted for virus by immunofluores- cent antibody examination. A negative fluorescent test removes the need to treat the bite victim either actively or passively. 33-36. The answers are 33-c, 34-d, 35-e, 36-b. (Gorbach, 2/e, pp 1334-1335, 1387, 1648, 1692.) Parvovirus B19 is the agent responsible for erythema infectiosum, also known as fifth disease. This disease most com- monly affects children between the ages of 5 and 14 years, but it can also occur in adults. The disease is characterized by a slapped-cheek rash, which may follow a prodrome of low-grade fever. A diffuse lacelike rash may also occur. Complications in adults include arthralgias, arthritis, aplastic crisis in patients with chronic hemolytic anemia, spontaneous abortion, and hydrops fetalis. Desquamation of the skin usually occurs during or after recovery from toxic shock syndrome (associated with a toxin produced by S. aureus). Peeling of the skin is also seen in Kawasaki disease, scarlet fever, and some severe drug reactions. Petechial rashes are often seen with potentially life-threatening infections, including meningo- coccemia, gonococcemia, rickettsial disease, infective endocarditis, atypi- cal measles, and disseminated intravascular coagulation (DIC) associated with sepsis. Infectious mononucleosis is the usual manifestation of infec- tion with Epstein-Barr virus. Since it is a viral disease, antibiotic therapy is not indicated. A diffuse maculopapular rash has been observed in over 90% of patients with infectious mononucleosis who are given ampicillin. The rash does not represent an allergic reaction to β-lactam antibiotics. 37-41. The answers are 37-e, 38-d, 39-c, 40-b, 41-a. (Mandell, 5/e, pp 1555, 1776-1780, 1801-1807.) Although salivary adenitis is the most prominent feature of the communicable disease of viral origin, mumps, involvement of the gonads, meninges, and pancreas is not uncommon. Males who develop mumps after puberty have a 20 to 35% chance of developing a painful orchitis. Central nervous system involvement is com- mon but usually mild, with 50% of cases causing an increase in lympho- cytes detectable in the CSF. Myocarditis, thrombocytopenic purpura, and polyarthritis may also occur as complications of this disease. An inflamma- tory change in the pancreas is a potentially serious problem; symptoms consist of abdominal discomfort and a gastroenteritis-like illness. Although a polyneuritis and a transverse myelitis have been described, the most common manifestation of CNS infection with varicella (chickenpox) is acute cerebellar ataxia. While chickenpox is usually a benign illness in chil- dren, other complications such as myocarditis, iritis, nephritis, orchitis, and hepatitis may occur. Pneumonitis occurs more commonly in adults than children. It can be difficult to distinguish between the vesicular lesions of small- pox and chickenpox. Classically, however, a history of rash with vesicles that develop over a few hours would be typical of a chickenpox infection; vesiculation that develops over a period of days is the rule in smallpox. While fever is characteristic of the prodrome of smallpox, it subsides prior to focal eruptions. Lesions of smallpox are typically all at the same stage of development, in contrast to the various stages seen in a patient with chickenpox. Preparations of vesicular fluid under electron microscopy show characteristic brick-shaped particles with poxvirus. A more readily available test, the Tzanck smear, performed by scraping the base of the lesion, should reveal multinucleated giant cells microscopically in a patient with chickenpox. Humoral immunity appears to be very important in the recovery from enteroviral infections. One of the most common complica- tions for patients with sex-linked or acquired agammaglobulinemia is a chronic central nervous system infection with an echovirus. In the absence of the ability to produce antibodies, this virus spreads rapidly and usually produces a fatal illness. The administration of intravenous preparations of gamma globulin intraventricularly has controlled this serious complication of immune deficiency in some patients. It may take from 9 to 11 days after exposure for the first symptoms of measles to develop. Malaise, irritability, and a high fever often associated with conjunctivitis with prominent tearing are common symptoms. This prodromal syndrome may last from 3 days to 1 week before the character- istic rash of measles develops. One or two days before the onset of the rash, characteristic Koplik spots (small, red, irregular lesions with blue-white centers) may be visible on the mucous membranes and occasionally on the conjunctiva. Classically, the measles rash will begin on the forehead and spread downward, and the Koplik spots will rapidly resolve. 42-46. The answers are 42-a, 43-d, 44-b, 45-e, 46-c. (Braunwald, 15/e, pp 1880-1896.) Pneumonia due to P. carinii was among the first rec- ognized manifestations of AIDS. The chest radiograph typically shows a diffuse bilateral interstitial pattern, but other patterns, including a normal radiograph, may occur. Pneumocystis infection may also occur at extrapul- monary sites. Cytomegalovirus (CMV) is a frequent disseminated pathogen that causes retinitis that may lead to blindness. CMV may also cause pneu- monitis, adrenalitis, and hepatitis, as well as colitis with significant diar- rhea. The protozoan Cryptosporidium may cause a chronic diarrhea that leads to malabsorption and wasting. It can be diagnosed by direct examination of the stool with special concentration or staining techniques or both. Salmonella infections have been recognized with increased frequency in patients with HIV. These patients are typically bacteremic and develop bacteremic relapse; they do not usually present with a diarrheal illness. Patients who present with seizures warrant evaluation for toxoplasmosis. CNS lymphoma and certain other infections may also cause seizures. Patients with toxoplasmic encephalitis may also have toxoplasmic chorioretinitis, although CMV remains the most common identified cause of retinitis in patients with AIDS. 47-51. The answers are 47-c, 48-b, 49-e, 50-d, 51-a. (Braunwald, 15/e, pp 936-937, 1050-1052, 1230.) Treatment of gonococcal infections should be guided by the increasing frequency of antibiotic-resistant Neisse- ria gonorrhoeae and high frequency of co-infection with Chlamydia tra- chomatis. Because of the increased frequency of resistance to penicillin and tetracyclines, ceftriaxone is recommended as the treatment of choice. Doxycycline is added to treat chlamydial and other causes of nongonococ- cal urethritis. First episodes of genital herpes may be particularly severe. Oral acyclovir will accelerate the healing but will not reduce the risk of recurrence once the drug is stopped. Trichomoniasis is usually diagnosed by a wet preparation microscopic examination or by culture. Both the patient and sexual partner should be treated with metronidazole. Penicillin remains the drug of choice for treatment of syphilis. The route of adminis- tration and duration of therapy depend on the stage of disease and pres- ence of CNS involvement and may also be influenced by the HIV serostatus of the patient.

Infectious disease Questions 2

 Infectious disease

25.  You are a physician in charge of the patients who reside in a nursing home. Several of the patients have developed influenza-like symptoms, and the community is in the midst of an influenza A outbreak. None of the nursing home residents have received the influenza vaccine. What course of action is most appropriate?
a.  Give the influenza vaccine to all residents who do not have a contraindication
    to the vaccine (i.e., allergy to eggs)
b.  Give the influenza vaccine to all residents who do not have a contraindication
    to the vaccine; also give amantadine for 2 weeks
c.  Give amantadine alone to all residents
d.  Do not give any prophylactic regimen

26.  An  elderly  male  develops  fever  3  days  after  cholecystectomy.  He
becomes short of breath, and chest x-ray shows a new right lower lobe
infiltrate. Sputum Gram stain shows gram-positive cocci in clumps, and
preliminary culture results suggest staphylococci. The initial antibiotic of
choice is
a.  Penicillinase-resistant penicillin such as nafcillin
b.  Vancomycin
c.  Antibiotic therapy should be based on the incidence of methicillin-resistant
    staphylococci in that hospital
d.  Quinolones have become the drug of choice for pneumonia

27.  A 30-year-old male with sickle cell anemia is admitted with cough,
rusty sputum, and a single shaking chill. Physical examination reveals
increased tactile fremitus and bronchial breath sounds in the left posterior
chest. The patient is able to expectorate a purulent sample. Which of the
following best describes the role of sputum Gram stain and culture?
a.  Sputum Gram stain and culture lack the sensitivity and specificity to be of value
    in this setting
b.  If the sample is a good one, sputum culture is useful in determining the anti-
    biotic sensitivity pattern of the organism, particularly Streptococcus pneumoniae
c.  Empirical use of antibiotics for pneumonia has made specific diagnosis unnec-
    essary
d.  There is no characteristic Gram stain in a patient with pneumococcal pneumonia

28.  A 30-year-old man who has spent 5 of the last 10 years in prison in New York City is referred from the prison because of hemoptysis. He has a history of tuberculosis diagnosed 3 years ago and took isoniazid and rifampin for about a month. A cavitary lesion is seen on chest x-ray. The physician should do all the following except
a.  Obtain sputum for acid-fast bacilli (AFB) stain, culture, and sensitivity
b.  Start supervised isoniazid and rifampin administration
c.  Start  a  supervised  multiple  drug  combination  to  treat  multidrug-resistant
    tuberculosis
d.  Place the patient in respiratory isolation
e.  Perform routine screening of inmates and staff for tuberculosis

29.  A recent outbreak of severe diarrhea is currently being investigated. Several children developed bloody diarrhea, and one remains hospitalized with acute renal failure. A preliminary investigation has determined that all the affected children ate at the same restaurant. The food they consumed was most likely to be
a.  Pork chops
b.  Hamburger
c.  Gefilte fish
d.  Sushi
e.  Soft-boiled eggs

30.  A 40-year-old female nurse was admitted to the hospital because of fever to 103°F. Despite a thorough workup in the hospital for over 3 weeks, no etiology has been found, and she continues to have temperature spikes greater than 102°F. The least likely diagnosis in this patient is
a.  Occult bacterial infection
b.  Influenza
c.  Lymphoma
d.  Adult Still’s disease
e.  Factitious fever

31.  In a patient who has mitral valve insufficiency, which procedure does not require prophylactic antibiotic therapy?
a.  Cardiac catheterization
b.  Prostatectomy
c.  Cystoscopy
d.  Tonsillectomy
e.  Periodontal surgery

32.  Rabies, an acute viral disease of the mammalian central nervous system, is transmitted by infective secretions, usually saliva. Which of the following statements about this disease is correct?
a.  The disease is caused by a reovirus that elicits both complement-fixing and
    hemagglutinating antibodies useful in the diagnosis of the disease
b.  The incubation period is variable, and, although 10 days is the most common
    elapsed time between infection and symptoms, some cases remain asympto-
    matic for 30 days
c.  Only 30% of infected patients will survive
d.  In the United States, the skunk and the raccoon have been important recent
    sources of human disease
e.  Wild animals that have bitten and are suspected of being rabid should be killed
    and their brains examined for virus particles by electron microscopy

Items 33-36
Match each clinical description with the appropriate infectious agent.
a.  Herpes simplex virus
b.  Epstein-Barr virus
c.  Parvovirus B19
d.  Staphylococcus aureus
e.  Neisseria meningitidis

33.  Slapped-cheek rash

34.  Desquamation of skin on hands and feet

35.  Petechiae on trunk
36.  Diffuse rash after administration of ampicillin Items 37-41
Match the following diseases with their appropriate signs or associations.
a.  Koplik spots
b.  Agammaglobulinemia
c.  A vesicular and pustular eruption that begins when the patient is afebrile
d.  Acute cerebellar ataxia
e.  Pancreatitis

37.  Mumps (CHOOSE 1 SIGN)

38.  Chickenpox (CHOOSE 1 SIGN)

39.  Smallpox (CHOOSE 1 SIGN)
40.  Echovirus infection (CHOOSE 1 SIGN)

41.  Measles (CHOOSE 1 SIGN)


Items 42-46
Match the clinical illness with the appropriate opportunistic pathogen in patients with AIDS.
a.  Pneumocystis carinii
b.  Toxoplasma gondii
c.  Cryptosporidium
d.  Cytomegalovirus
e.  Salmonella    

42.  Pneumonia (CHOOSE 1 PATHOGEN)

43.  Retinitis (CHOOSE 1 PATHOGEN)

44.  Seizures (CHOOSE 1 PATHOGEN)

45.  Bacteremia (CHOOSE 1 PATHOGEN)

46.  Diarrhea  diagnosed  by  direct  examination  of  stool    (CHOOSE  1
PATHOGEN)

Items 47-51
For each of the sexually transmitted diseases, select the treatment of choice.
a.  Penicillin
b.  Doxycycline
c.  Ceftriaxone plus doxycycline
d.  Metronidazole
e.  Acyclovir

47.  Presumed gonococcal urethritis (SELECT 1 TREATMENT)
48.  Nongonococcal urethritis (SELECT 1 TREATMENT)

49.  Severe primary genital herpes (SELECT 1 TREATMENT)

50.  Trichomoniasis (SELECT 1 TREATMENT)

51.  Syphilis (SELECT 1 TREATMENT)

Items 52-55
Identify the antimicrobial agent associated with the adverse effects listed below.
a.  Gentamicin
b.  Imipenem
c.  Tetracycline
d.  Clindamycin

52.  Photosensitivity (CHOOSE 1 AGENT)

53.  Acute tubular necrosis (CHOOSE 1 AGENT)

54.  Progressive weakness in a patient with myasthenia gravis (CHOOSE 1 AGENT)

55.  Seizures (CHOOSE 1 AGENT)

56.  A previously healthy 25-year-old music teacher develops fever and a rash over her face and chest. The rash is itchy and on exam involves multiple papules and vesicles in varying stages of development. One week later she complains of cough and is found to have an infiltrate on x-ray. The most likely etiology of the infection is
a.  Streptococcus pneumoniae
b.  Mycoplasma pneumoniae
c.  Pneumocystis carinii
d.  Varicella virus

Items 57-58
57.  A  22-year-old  male  complains  of  fever  and  shortness  of  breath. There is no pleuritic chest pain or rigors and no sputum production. A chest x-ray shows diffuse perihilar infiltrates. The patient worsens while on erythromycin. A silver methenamine stain shows cystlike structures. Which of the following is correct?
a.  Definitive diagnosis can be made by serology
b.  The organism will grow after 48 h
c.  History will likely provide important clues to the diagnosis
d.  Cavitary disease is likely to develop

Infectious disease Answers 1

iRAN Infectious Disease Answers

Meysam Amiri 27/01/2011 pm

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Refrence: Med.Science Laboratories Journal

Soon! Infectious Disease Questions 1

Infectious Disease

Questions

DIRECTIONS:   Each item below contains a question or incomplete statement followed by suggested responses. Select the one best response to each question.
1.  A 30-year-old male patient complains of fever and sore throat for several days. The patient presents to you today with additional complaints of hoarseness, difficulty breathing, and drooling. On examination, the patient is febrile and has inspiratory stridor. Which of the following is the best course of action?
a.  Begin outpatient treatment with ampicillin
b.  Culture throat for β-hemolytic streptococci
c.  Admit to intensive care unit and obtain otolaryngology consultation
d.  Schedule for chest x-ray

2.  A 70-year-old patient with long-standing type 2 diabetes mellitus pre-
sents with complaints of pain in the left ear with purulent drainage. On
physical exam, the patient is afebrile. The pinna of the left ear is tender, and
the external auditory canal is swollen and edematous. The peripheral white
blood cell count is normal. The organism most likely to grow from the puru-
lent drainage is
a.  Pseudomonas aeruginosa
b.  Staphylococcus aureus
c.  Candida albicans
d.  Haemophilus influenzae
e.  Moraxella catarrhalis




Items 3-4
A 25-year-old male student presents with the chief complaint of rash. There is no headache, fever, or myalgia. A slightly pruritic maculopapular rash is noted over the abdomen, trunk, palms of the hands, and soles of the feet. Inguinal, occipital, and cervical lymphadenopathy is also noted. Hypertrophic, flat, wartlike lesions are noted around the anal area. Laboratory studies show the following:
Hct: 40%
Hgb: 14 g/dL
WBC: 13,000/µL
Diff:
Segmented neutrophils: 50%
Lymphocytes: 50%

3.  The most useful laboratory test in this patient is
a.  Weil-Felix titer
b.  Venereal Disease Research Laboratory (VDRL) test
c.  Chlamydia titer
d.  Blood cultures

4.  The treatment of choice for this patient is
a.  Penicillin
b.  Ceftriaxone
c.  Tetracycline
d.  Interferon α
e.  Erythromycin



Items 5-7
A 20-year-old female college student presents with a 5-day history of cough, low-grade fever (temperature 100°F), sore throat, and coryza. On exam, there  is  mild  conjunctivitis  and  pharyngitis.  Tympanic  membranes  are inflamed, and one bullous lesion is seen. Chest exam shows few basilar rales. Laboratory findings are as follows:
Hct: 38
WBC: 12,000/µL
Lymphocytes: 50%
Mean corpuscular volume (MCV): 83 nL Reticulocytes: 3% of red cells
CXR: bilateral patchy lower lobe infiltrates
5.  The sputum Gram stain is likely to show
a.  Gram-positive diplococci
b.  Tiny gram-negative coccobacilli
c.  White blood cells without organisms
d.  Acid-fast bacilli

6.  This patient is likely to have
a.  High titers of adenovirus
b.  High titers of IgM cold agglutinins
c.  A positive silver methenamine stain
d.  A positive blood culture for Streptococcus pneumoniae

7.  Treatment of choice is
a.  Erythromycin
b.  Supportive therapy
c.  Trimethoprim-sulfamethoxazole
d.  Cefuroxime

Items 8-10
A 19-year-old male presents with a 1-week history of malaise and anorexia
followed by fever and sore throat. On physical examination, the throat is
inflamed without exudate. There are a few palatal petechiae. Cervical
adenopathy is present. The liver is percussed at 12 cm and the spleen is
palpable.
Throat culture: negative for group A streptococci Hct: 38%
Hgb: 12 g/dL
Reticulocytes: 4%
WBC: 14,000/µL
Segmented: 30%
Lymphocytes: 60%
Monocytes: 10%
Bilirubin total: 2.0 mg/dL (normal 0.2 to 1.2)
Lactic dehydrogenase (LDH) serum: 260 IU/L (normal 20 to 220) Aspartate (AST): 40 U/L (normal 8 to 20 U/L)
Alanine (ALT): 35 U/L (normal 8 to 20 U/L)
Alkaline phosphatase: 40 IU/L (normal 35 to 125)

8.  The most important initial test is
a.  Liver biopsy
b.  Strep screen
c.  Peripheral blood smear
d.  Toxoplasmosis IgG
e.  Lymph node biopsy

9.  The most important serum test is
a.  Heterophile antibody
b.  Hepatitis B IgM
c.  Cytomegalovirus IgG
d.  ASLO titer
e.  Hepatitis C antibody

10.  Corticosteroids would be indicated if
a.  Liver function tests worsen
b.  Fatigue lasts more than 1 week
c.  Severe hemolytic anemia is demonstrated
d.  Hepatitis B is confirmed



DIRECTIONS:   Each  group  of  questions  below  consists  of  lettered
options followed by a set of numbered items. For each numbered item,
select the one lettered option with which it is most closely associated. Each
lettered option may be used once, more than once, or not at all.

Items 11-14
Match the clinical description with the most likely organism.
a.  Streptococcus pneumoniae
b.  Staphylococcus aureus
c.  Viridans streptococci
d.  Providencia stuartii
e.  Actinomyces israelii
f.  Haemophilus ducreyi
g.  Neisseria meningitidis
h.  Listeria monocytogenes

11.  A 30-year-old female with mitral valve prolapse and mitral regurgitant murmur develops fever, weight loss, and anorexia after undergoing a dental procedure. (CHOOSE 1 ORGANISM)

12.  An     80-year-old-male,  hospitalized  for  hip  fracture,  has  a  Foley
catheter in place when he develops shaking chills, fever, and hypotension.
(CHOOSE 1 ORGANISM)

13.  A young man develops a painless, fluctuant purplish lesion over the mandible. Cutaneous fistula is noted after several weeks.  (CHOOSE  1 ORGANISM)
14.  A sickle cell anemia patient presents with high fever, toxicity, signs of pneumonia, and stiff neck. (CHOOSE 1 ORGANISM)


Items 15-18
Select an antiviral agent for each patient.
a.  Ganciclovir
b.  Acyclovir
c.  Interferon α
d.  Didanosine
e.  Ribavirin
f.  Amantadine
g.  Vidarabine
h.  Zalcitabine

15.  A military recruit develops pneumonia secondary to influenza A. Symptoms began 24 h prior to physician visit. (SELECT 1 AGENT)

16.  An HIV-positive patient with a CD4 count of 50 complains of the onset of visual blurring; opacity is seen on funduscopic exam. (SELECT 1 AGENT)

17.  A sexually active young woman has anogenital warts and requests intralesional therapy. (SELECT 1 AGENT)
18.  An infant with respiratory syncytial virus infection requires mechanical ventilation. (SELECT 1 AGENT)

Items 19-21
Select the fungal agent most likely responsible for the disease process described.
a.  Histoplasma capsulatum
b.  Blastomycosis dermatitidis
c.  Coccidioides immitis
d.  Cryptococcus neoformans
e.  Candida albicans
f.  Aspergillus fumigatus
g.  Zygomycosis


19.  A  young,  previously  healthy  male  presents  with  verrucous  skin lesions, bone pain, fever, cough, and weight loss. Chest x-ray shows nodular infiltrates. (SELECT 1 AGENT)
20.  A diabetic patient is admitted with elevated blood sugar and acidosis. The patient complains of headache and sinus tenderness and has black, necrotic material draining from the nares. (SELECT 1 AGENT)
21.  A young woman presents with asthma and eosinophilia. Fleeting pul-
monary infiltrates occur with bronchial plugging. (SELECT 1 AGENT)

Items 22-24
A 40-year-old male develops bilateral facial weakness after returning from
a camping trip in Wisconsin that lasted 6 weeks. The patient gives a history
of arthralgias. On exam, he cannot close either eye well or raise either eye-
brow. The first heart sound is diminished. There is no evidence of arthritis.
Hgb: 14 g /dL
WBC: 10,000/µL
VDRL: negative
FTA-Abs: positive
ECG: first-degree AV block

22.  Which of the following would be most useful?
a.  CT scan of head
b.  MRI of head
c.  More detailed history
d.  Kveim test

23.  The likely cause of these symptoms is
a.  Intracranial infection
b.  Lyme disease
c.  Endocarditis
d.  Herpes simplex

  Treatment of choice is .24
a.  Penicillin or ceftriaxone
b.  Acyclovir
c.  Corticosteroids
d.  Aminoglycoside

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virus 4

virus 4

Latency

Inapparent infections (those that do not cause specific signs and symptoms) often result after exposure to picornaviruses, influenza viruses, rhinoviruses, herpesviruses, and adenoviruses but less frequently to measles and chickenpox viruses. In cases of inapparent infection, long-lasting immunity develops, but only to the strain of virus that has the same antigenic composition as the original infecting virus.

Certain of these viruses persist in the tissues of the host after the initial infection despite the presence of circulating antibodies to it in the blood and tissues. Such viruses probably reside inside cells, where they are protected from antibodies that cannot penetrate the cell membrane. Among persistent viruses are adenoviruses, measles virus, and, in particular, many kinds of herpesviruses. The genetic information of herpesviruses and adenoviruses can be integrated into the genome of the host cell, but it is believed that these viruses frequently, and the measles virus invariably, reside in cells in the form of extrachromosomal genes (genes not integrated in chromosomes). These dormant viruses can be activated by many factors, such as trauma, another infection, emotional stress, menstruation, excessive exposure to sunlight, and various illnesses.

The phenomenon of latency and reactivation is particularly common among viruses of the family Herpesviridae, which cause chronic or recurrent diseases: (1) herpes simplex virus type 1, which causes recurrent cold sores, (2) herpes simplex virus type 2 in genital tissue, which causes repeated herpetic infections of the vagina or penis, (3) cytomegalovirus, which usually produces an inapparent infection activated by simultaneously occurring disease to cause severe liver, lung, or nervous-system disease, and (4) varicella virus, which is the causative agent of chickenpox but which can be activated decades later to produce herpes zoster (shingles). A rare, but invariably fatal, disease of the nervous system is subacute sclerosing panencephalitis (SSPE), which is a progressive, degenerative condition caused by measles virus (a paramyxovirus) lying dormant in brain cells for many years and then reactivated, usually in adolescence. There is no simple explanation for why latent viruses, such as those in the family Herpesviridae, that are present in the tissues of most adult humans can be activated to cause disease in some people but not in others.

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virus 3

Viral DNA integration

Lysogeny

Many bacterial and animal viruses lie dormant in the infected cell, and their DNA may be integrated into the DNA of the host cell chromosome. The integrated viral DNA replicates as the cell genome replicates; after cell division, the integrated viral DNA is duplicated and usually distributed equally to the two cells that result. The bacteria that carry the noninfective precursor phage, called the prophage, remain healthy and continue to grow until they are stimulated by some perturbing factor, such as ultraviolet light. The prophage DNA is then excised from the bacterial chromosome, and the phage replicates, producing many progeny phages and lysing the host bacterial cell. This process, originally discovered in temperate bacteriophages in 1950 by the French microbiologist André Lwoff, is called lysogeny.

The classic example of a temperate bacteriophage is called lambda (λ) virus, which readily causes lysogeny in certain species of the bacterium Escherichia coli. The DNA of the λ bacteriophage is integrated into the DNA of the E. coli host chromosome at specific regions called attachment sites. The integrated prophage is the inherited, noninfectious form of the virus; it contains a gene that represses the lytic functions of the phage and thus assures that the host cell will continue to replicate the phage DNA along with its own and that it will not be destroyed by the virus. Ultraviolet light, or other factors that stimulate the replication of DNA in the host cell, causes the formation of a recA protease, an enzyme that breaks apart the λ phage repressor and induces λ phage replication and, eventually, destruction of the host cell.

Excision of the prophage DNA from the host chromosomal DNA (as an initial step in the synthesis of an infective, lytic virus) sometimes results in the removal of some of the host cell DNA, which is packaged into defective bacteriophages; part of the bacteriophage DNA is removed and replaced at the other end by a gene of the host bacterium. Such a virus particle is called a transducing phage because, when it infects a bacterial cell, it can transmit the gene captured by λ phage DNA into the next bacterial cell it infects. Transduction by bacteriophages is an efficient means for transferring the genetic information of one bacterial cell to another.

This means of transferring genetic information, called lysogenic conversion, imparts genes with special functions to bacterial cells without such functions. It is common in bacteria and is an important aspect of the epidemiology (incidence, distribution, and control) of infectious diseases. For example, the bacterium Corynebacterium diphtheriae is the causative agent of diphtheria, but only when it contains the prophage of bacteriophage β, which codes for the toxin that is responsible for the disease.

 

Malignant transformation

A phenomenon analogous to bacterial cell lysogeny occurs in animal cells infected with certain viruses. These animal viruses do not generally cause disease immediately for certain animal cells. Instead, animal cells are persistently infected with such viruses, the DNA of which (provirus) is integrated into the chromosomal DNA of the host cell. In general, cells with integrated proviral DNA are converted into cancer cells, a phenomenon known as malignant transformation. As is the case with bacterial prophages, the transformed animal cell contains no infectious virus but only the integrated provirus DNA, which replicates along with the dividing cell's chromosomes. Therefore, following mitosis of the transformed cell, each new cell receives a copy of the proviral DNA. The hallmark of these transformed animal cells is that their growth is uncontrollable; unlike normal cells, their growth is not inhibited by contact with other cells, and they lose their capacity to adhere (anchor) to certain surfaces. Growth of normal tissues and organs is also controlled by a genetic phenomenon called programmed cell death, or apoptosis, in which a certain number of cells will die and be eliminated after a finite number of divisions. Malignant transformation can impede programmed cell death, thus allowing the cells to grow uncontrolled, resulting in cancer.

Among the animal viruses that cause malignant transformation by integration of proviral DNA are several families of DNA viruses and one large family of RNA viruses, the Retroviridae. Viruses of the family Papovaviridae were perhaps the first to be associated with malignancy (causing death or illness) in animals. Polyomavirus is widespread in mice; it can infect other rodents, and it can cause tumours in infected animals. Another virus of the family Papovaviridae is simian virus 40 (SV40), originally isolated from cells of the African green monkey (Cercopithecus sabaeus), where it grows rapidly and kills the cells. Infection of rodent or human cells, however, results in an abortive infection (an incompatibility between the virus and the host cell) but sometimes induces malignancy (sarcomas or lymphomas) in the occasional cell that is transformed. Viruses related to polyomavirus and SV40 have been isolated from humans, one of which, the JC virus, appears to be the causative agent of a fatal neurological disease called progressive multifocal leukoencephalopathy. In general, however, the human papovaviruses are not clearly associated with disease.

Other viruses of the family Papovaviridae include the papillomaviruses, which are also small polygonal viruses containing circular double-stranded DNA. The papillomaviruses are associated with usually benign (nonthreatening) but widespread tumours, called papillomas or polyps, occurring in human skin and the genital tract. Specific papillomaviruses have been identified in humans in common warts and in genital warts (condylomata acuminata). Cancers of the human genital tract, particularly uterine cancer of the cervix, are frequently found in association with human papillomavirus type 16 (HPV 16); the virus undoubtedly is transmitted as a venereal disease.

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Infectious Disease

Questions

  Answers, Explanations, and References

virus 2

virus 2

By far the best-studied example of a helical rod-shaped virus is the tobacco mosaic virus, which was crystallized by Wendell Stanley in 1935. The tobacco mosaic virus contains a genome of single-stranded RNA encased by 2,130 molecules of a single protein; there are 16¹/₃ protein molecules for each turn of the RNA helix in the ratio of three nucleotides for each protein molecule.

Under the right environmental conditions, viral RNA and protein molecules in liquid suspension will assemble themselves into a perfectly formed and fully infectious virus. The length of the helical virus capsid is determined by the length of the nucleic acid molecule, which is the framework for the assembly of the capsid protein. The various helical viruses have different lengths and widths depending on the size of the nucleic acid as well as on the mass and shape of the protein molecule. Some of these helical viruses form rigid rods, while others form flexible rods, depending on the properties of the assembled proteins.

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virus 1

virus

Introduction

an infectious agent of small size and simple composition that can multiply only in living cells of animals, plants, or bacteria. The name is from a Latin word meaning “slimy liquid” or “poison.”

The earliest indications of the biological nature of viruses came from studies in 1892 by the Russian scientist Dmitry I. Ivanovsky and in 1898 by the Dutch scientist Martinus W. Beijerinck. Beijerinck first surmised that the virus under study was a new kind of infectious agent, which he designated contagium vivum fluidum, meaning that it was a live, reproducing organism that differed from other organisms. Both of these investigators found that a disease of tobacco plants could be transmitted by an agent, later called tobacco mosaic virus, passing through a minute filter that would not allow the passage of bacteria. This virus and those subsequently isolated would not grow on an artificial medium and were not visible under the light microscope. In independent studies in 1915 by the British investigator Frederick W. Twort and in 1917 by the French Canadian scientist Félix H. d'Hérelle, lesions in cultures of bacteria were discovered and attributed to an agent called bacteriophage (“eater of bacteria”), now known to be viruses that specifically infect bacteria.

The unique nature of these organisms meant that new methods and alternative models had to be developed to study and classify them. The study of viruses confined exclusively or largely to humans, however, posed the formidable problem of finding a susceptible animal host. In 1933 the British investigators Wilson Smith, Christopher H. Andrewes, and Patrick P. Laidlaw were able to transmit influenza to ferrets, and the influenza virus was subsequently adapted to mice. In 1941 the American scientist George K. Hirst found that influenza virus grown in tissues of the chicken embryo could be detected by its capacity to agglutinate (draw together) red blood cells.

A significant advance was made by the American scientists John Enders, Thomas Weller, and Frederick Robbins, who in 1949 developed the technique of culturing cells on glass surfaces; cells could then be infected with the viruses that cause polio (poliovirus) and other diseases. (Until this time, the poliovirus could be grown only in the brains of chimpanzees or the spinal cords of monkeys.) Culturing cells on glass surfaces opened the way for diseases caused by viruses to be identified by their effects on cells (cytopathogenic effect) and by the presence of antibodies to them in the blood. Cell culture then led to the development and production of vaccines (preparations used to elicit immunity against a disease) such as the poliovirus vaccine.

Scientists were soon able to detect the number of bacterial viruses in a culture vessel by measuring their ability to break apart (lyse) adjoining bacteria in an area of bacteria (lawn) overlaid with an inert gelatinous substance called agar—viral action that resulted in a clearing, or “plaque.” The American scientist Renato Dulbecco in 1952 applied this technique to measuring the number of animal viruses that could produce plaques in layers of adjoining animal cells overlaid with agar. In the 1940s the development of the electron microscope permitted individual virus particles to be seen for the first time, leading to the classification of viruses and giving insight into their structure.

Advancements that were made in chemistry, physics, and molecular biology since the 1960s have revolutionized the study of viruses. For example, electrophoresis on gel substrates gave a deeper understanding of the protein and nucleic acid composition of viruses. More-sophisticated immunologic procedures, including the use of monoclonal antibodies directed to specific antigenic sites on proteins, gave a better insight into the structure and function of viral proteins. The progress made in the physics of crystals that could be studied by X-ray diffraction provided the high resolution required to discover the basic structure of minute viruses. Applications of new knowledge about cell biology and biochemistry helped to determine how viruses use their host cells for synthesizing viral nucleic acids and proteins.

The revolution that took place in the field of molecular biology allowed the genetic information encoded in nucleic acids of viruses—which enables viruses to reproduce, synthesize unique proteins, and alter cellular functions—to be studied. In fact, the chemical and physical simplicity of viruses has made them an incisive experimental tool for probing the molecular events involved in certain life processes.

This article discusses the fundamental nature of viruses: what they are, how they cause infection, and how they may ultimately cause disease or bring about the death of their host cells. For more-detailed treatment of specific viral diseases, see infection.

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Respiratory disease 7

Disability and attribution of occupational lung diseases

Occupational lung diseases are of social and legal importance. In such cases, respiratory specialists must assess the extent of an individual's disability and then form an opinion on whether an individual's disability can be attributed to an occupational hazard. Pulmonary function testing and tests of exercise capability provide a good indication of the impact of a disease on the physical ability of a patient. However, it is much more difficult to decide how much of a patient's disability is attributable to occupational exposure. If the exposure is historically known to cause a specific lesion in a significant percentage of exposed persons, such as mesothelioma in workers exposed to asbestos, attribution may be fairly straightforward. In many cases, however, the exposure may cause only generalized pulmonary changes or lung lesions for which the precise cause cannot be determined. These instances may be complicated by a history of cigarette smoking. Physicians asked to present opinions on attributability before a legal body frequently must rely on the application of probability statistics to the individual case, a not wholly satisfactory procedure.

 

Miscellaneous conditions of the respiratory system

Idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis is also known as cryptogenic fibrosing alveolitis. This is a generally fatal lung disease of unknown cause that is characterized by progressive fibrosis of the alveolar walls. The disease most commonly manifests between the ages of 50 and 70, with insidious onset of shortness of breath on exertion. A dry cough is common as well. Sharp crackling sounds, called rales or “Velcro crackles,” are heard through a stethoscope applied to the back in the area of the lungs. Computerized tomography (CT) imaging shows fibrosis and cysts that characteristically form in a rim around the lower outer portions of both lungs. In addition, pulmonary function testing shows a reduction in lung volume. Lung biopsies confirm the diagnosis by showing fibrosis with a lack of inflammation.

The disease causes progressive shortness of breath with exercise and ultimately produces breathlessness at rest. Hypoxemia (decreased levels of oxygen in the blood) initially occurs with exercise and later at rest and can be severe. Some individuals have clubbed fingertips and toes. The average duration of survival from diagnosis is four to six years; however, some people live 10 years or longer. Aside from administration of supplemental oxygen, there is no effective treatment. Some individuals may benefit from single or double lung transplantation (see above Lung transplantation).

 

Sarcoidosis

Sarcoidosis is a disease of unknown cause characterized by the development of small aggregations of cells, or granulomas, in different organs; the lung is commonly involved. Other common changes are enlargement of the lymph glands at the root of the lung, skin changes, inflammation in the eye, and liver dysfunction; occasionally there is inflammation of nerve sheaths, leading to signs of involvement in the affected area. The kidney is not commonly involved, but some changes in blood calcium levels occur in a small percentage of cases. In most cases the disease is first detected on chest radiographs. Evidence of granulomas in the lung may be visible, but often there is little interference with lung function. The disease usually remits without treatment within a year or so, but in a small proportion of cases it progresses, leading finally to lung fibrosis and respiratory failure. The granulomatous inflammation in sarcoidosis can be controlled by long-term administration of a corticosteroid such as prednisone.

 

Eosinophilic granuloma

Also known as pulmonary histiocytosis X, this disease causes granulomas associated with eosinophil cells, a subgroup of the white blood cells. It sometimes also causes lesions in bone. Eosinophilic granuloma is a lung condition that may spontaneously “burn out,” leaving the lung with some permanent cystic changes. Its cause is not known; however, the incidence is greatly increased in cigarette smokers.

 

Pulmonary alveolar proteinosis

Pulmonary alveolar proteinosis is a disease of unknown cause characterized by accumulation in the alveolar spaces of surfactant. Small amounts of this lipid- and protein-rich fluid normally line the surfaces of the alveoli, reducing surface tension and thereby keeping the air spaces open. Buildup of this liquid within the air spaces interferes with gas exchange and causes progressive shortness of breath. The only effective treatment of this disease is whole-lung lavage. Under general anesthesia, the bronchus leading to one lung is isolated, and that lung is filled with sterile salt water. Drainage of the fluid removes some of the excess surfactant. Flooding and drainage are repeated up to 20 or 30 times until little or no more surfactant is removed. Then on another day the opposite lung is treated. Whole-lung lavage may be required at 6- to 12-month intervals for several years before complete remission occurs.

 

Immunologic conditions

The lung is often affected by generalized diseases of the blood vessels. Wegener granulomatosis, an acute inflammatory disease of the blood vessels believed to be of immunologic origin, is an important cause of pulmonary blood vessel inflammation. Acute hemorrhagic pneumonitis occurring in the lung in association with changes in the kidney is known as Goodpasture syndrome. The condition has been successfully treated by exchange blood transfusion, but its cause is not fully understood. Pulmonary hemorrhage also occurs as part of a condition known as pulmonary hemosiderosis, which results in the accumulation of the iron-containing substance hemosiderin in the lung tissues. The lung may also be involved in a variety of ways in the disease known as systemic lupus erythematosus, which is also believed to have an immunologic basis. Pleural effusions may occur, and the lung parenchyma may be involved. These conditions have only recently been recognized and differentiated; accurate diagnosis has been much improved by refinements in radiological methods, by the use of pulmonary function tests, and especially by improvement in thoracic surgical techniques and anesthesia that have made lung biopsy much less dangerous than it formerly was.

The common condition of rheumatoid arthritis may be associated with scattered zones of interstitial fibrosis in the lung or with solitary isolated fibrotic lesions. More rarely, a slowly obliterative disease of small airways (bronchiolitis) occurs, leading finally to respiratory failure.

 

Radiation damage

The lung may be damaged by radiation therapy in the treatment of cancer of the breast and other conditions. About three weeks or so after the end of the treatment, a pneumonitis may develop in the underlying lung, signaled by an unproductive cough. The condition may resolve, but in a few cases the lung becomes fibrotic and contracts to a small fraction of its normal volume. There is considerable individual variation in the response to the same dose of radiation.

 

Circulatory disorders

The lung is commonly involved in disorders of the circulation. The most important and common of these is blockage of a branch of the pulmonary artery by blood clot, which has usually formed in the veins of the legs or of the pelvis. The resulting pulmonary embolism leads to changes in the lung supplied by the affected artery. When severe, these changes are known as a pulmonary infarction. The consequences of embolism range from sudden death, when the infarction is massive, to an increased respiratory rate, slight fever, and occasionally some pleuritic pain over the site of the infarction. An individual is at an increased risk for pulmonary embolism whenever his or her circulation is sluggish. This occurs most often during a postoperative period when the affected individual is immobilized in bed. Early mobilization after surgery or childbirth is considered an important preventive measure. Repetitive pulmonary emboli may lead to chronic pulmonary thromboembolism, in which the pressure in the main pulmonary artery is persistently increased. Over time, a clot is replaced with an adherent fibrous material in the pulmonary arteries, causing shortness of breath on exertion and, ultimately, right ventricular heart failure. The obstructing lesions can be surgically removed in some instances, thereby relieving symptoms of breathlessness.

In primary pulmonary hypertension, a condition of unknown origin, a marked increase in pulmonary arterial pressure occurs as a result of progressive narrowing and obliteration of small pulmonary arteries. Primary pulmonary hypertension leads to enlargement of the heart and eventual failure of the right ventricle of the heart, usually after increasing disability with severe shortness of breath. In addition to chest X-rays and basic pulmonary function tests, a diagnosis of pulmonary hypertension is often confirmed following an electrocardiogram (EKG) to assess electrical function of the heart, an echocardiogram to determine whether the heart is enlarged and to evaluate the flow of blood through the heart, and cardiac catheterization to measure pressure in the pulmonary artery and right ventricle of the heart.

Treatment of primary pulmonary hypertension is aimed at alleviating symptoms. Because of the variability in physiological response to certain drugs and because of the progressive nature of the disease, affected individuals require careful, long-term evaluation and treatment. While some medications such as calcium channel blockers may be taken orally, others such as prostacyclin are given by continuous intravenous infusion supplied through a portable battery-powered pump. Prostacyclin can sometimes be given in oral or inhaled forms. In some cases, lung transplantation is necessary.

Congestion of the lungs (pulmonary edema) and the development of fluid in the pleural cavity, with consequent shortness of breath, follows left ventricular failure, usually as a consequence of coronary arterial disease. When the valve between the left atrium of the heart and the left ventricle is thickened and deformed by rheumatic fever (mitral stenosis), chronic changes develop in the lung as a result of the increased pressure in the pulmonary circulation. These changes contribute to the shortness of breath and account for the blood staining of the sputum.

 

Acute respiratory distress syndrome of adults

Bacterial or viral pneumonia, exposure of the lung to gases, aspiration of material into the lung (including water in near-drowning episodes), or any generalized septicemia (blood poisoning) or severe lung injury may lead to sudden, widespread bilateral lung injury. This syndrome is known as acute respiratory distress syndrome of adults. It was recognized as “shock lung” in injured soldiers evacuated by helicopter to regional military hospitals during the Vietnam War. Many causes of respiratory distress syndrome of adults have been identified. Acute respiratory distress syndrome carries about a 50 percent mortality. Life-support treatment with assisted ventilation rescues many patients, although superimposed infection or multiple organ failure can result in death. Recovery and repair of the lung may take months after clinical recovery from the acute event.

 

Air pollution

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Respiratory disease 6

Occupational lung disease

Silicosis and black lung disease

Silica dust produces a distinctive reaction in the lung that eventually leads to the development of masses of fibrous tissue and distinctive nodules of dense fibrosis, which, by contracting, distort and damage the lung. Silicosis is a hazard in any occupation in which workers are exposed to silica dust, particularly rock drilling above or below ground, quarrying, or grinding with a wheel containing silica. Cases have also been reported in dental technicians, who use the material ground into a fine powder. Silicosis is usually fairly easy to detect on radiographs, and in its later stages it causes considerable shortness of breath and reduction of the vital capacity (a maximal breath). Sandblasting without respiratory protection is exceedingly dangerous, and fatal cases of acute silicosis caused by unprotected sandblasting have been reported. The dangers of silica are generally well recognized, and better protection has reduced the incidence of this condition. The disease may advance, with increasing disability, for years after the person has stopped inhaling the dust.

Coal dust alone, even if its silica content is very low, causes a distinctive pattern of change in the lung known as coalworker's pneumoconiosis (also called black lung). Initially the dust is deposited in the terminal bronchioles, where it causes a fibrotic reaction. At this stage there is little disability, but later the disease may progress to a more-generalized form, and in some instances large masses of fibrotic tissue form in the lung. This condition, known as progressive massive fibrosis, is usually associated with severe disability and the risk of secondary heart failure. It is not clear whether this stage is more likely to develop if pulmonary tuberculosis is superimposed on the respiratory damage caused by coal dust inhalation. There is no curative treatment for silicosis or black lung disease.

 

Asbestosis and mesothelioma

The widespread use of asbestos as an insulating material during World War II, and later in flooring, ceiling tiles, brake linings, and as a fire protectant sprayed inside buildings, led to a virtual epidemic of asbestos-related disease 20 years later. The first disease recognized to be caused by asbestos was asbestosis, which produces characteristic changes in the lungs that can be identified in chest X-rays and that can impair lung function at an early stage. Later it was discovered that exposure to much less asbestos than was needed to cause asbestosis led to thickening of the pleura, and, when both cigarette smoking and asbestos exposure occurred, there was a major increase in the risk for lung cancer. The risks from smoking and from significant asbestos exposure are multiplicative in the case of lung cancer. A malignant tumour of the pleura known as mesothelioma is caused almost exclusively by inhaled asbestos. Often a period of 20 years or more elapses between exposure to asbestos and the development of a tumour.

As far as is known, all the respiratory changes associated with asbestos exposure are irreversible. Malignant mesothelioma is rare and unrelated to cigarette smoking, but survival after diagnosis is less than two years. In most cases, thickening of the pleura is not associated with disturbance of lung function or with symptoms of exposure to asbestos, although in occasional cases pleuritis is very aggressive and thus may produce symptoms. It is not yet understood exactly why asbestos devastates the tissues of the lungs. Asbestos has been suspected to play a role in stimulating certain cellular events, such as the generation of harmful reactive molecules and the activation of damaging inflammatory processes. These events could contribute to the scarring and fibrosis that are characteristic of inhalation of asbestos fibres. Not all types of asbestos are equally dangerous; the risk of mesothelioma in particular appears to be much higher if crocidolite, a blue asbestos that comes from South Africa, is inhaled than if chrysotile is inhaled. But exposure to any type of asbestos is believed to increase the risk of lung cancer, especially when associated with cigarette smoking. While the removal of asbestos from buildings has greatly alleviated the risk of exposure to asbestos for many people, inhalation of asbestos remains a significant risk for the workers removing the material. All industrialized countries have imposed strict regulations for handling asbestos, and the workforce is generally aware of the material's dangers.

There is no curative therapy for asbestosis or mesothelioma. Treatment is aimed at managing symptoms, preventing infections, and delaying disease progression. Individuals with asbestosis often receive annual vaccinations against influenza and pneumococcal pneumonia. In some cases, aerosol medications that thin mucous secretions and oxygen that is supplied by a portable tank are necessary to maintain adequate oxygen intake. In other cases, lung transplantation is required. Individuals with mesothelioma often undergo chemotherapy and radiation therapy, which may prolong survival for a short period of time.

 

Respiratory toxicity of glass and metal fibres

The increasing use of man-made mineral fibres (as in fibreglass and rock wool) has led to concern that these may also be dangerous when inhaled; present evidence suggests that they do increase the risk of lung cancer in persons occupationally exposed to them. Standards for maximal exposure have been proposed.

The toxicity of beryllium was first discovered when it was widely used in the manufacture of fluorescent light tubes shortly after World War II. In susceptible individuals, beryllium causes the formation of granulomas in the lung and alveolar wall thickening, often with considerable disability as a result. Although beryllium is no longer used in the fluorescent light industry, it is still important in the manufacture of metal alloys and ceramics, and new cases of beryllium poisoning are occasionally reported.

 

Byssinosis and related diseases

It is not only inorganic minerals and dusts that may affect the lung. The dust produced in the processing of raw cotton, flax, or hemp may cause chronic obstructive lung disease. However, this does not have a characteristic pathology, and it does not give rise to emphysema. It is unclear whether the dust from the fibres alone or the combination of cigarette smoke and fibre dust is particularly dangerous. The disease that results is known as byssinosis, or “brown lung.” Workers in cotton plants in England used to complain of “Monday morning fever” and were found to suffer an easily measurable decrement in ventilatory function when they returned to work after spending a weekend away from the plant. The active particle or contaminant in the cotton dust that is responsible for the syndrome appears to be an endotoxin produced by bacteria in the fibres of cotton.

The dust from western red cedar may cause occupational asthma, and dust from the redwood and other trees may cause an acute hypersensitivity pneumonitis. Workers in the sugarcane industry may be affected by a similar syndrome, known as bagassosis; sisal workers also develop airflow obstruction.

 

Respiratory toxicity of industrial chemicals

Toluene diisocyanate, used in the manufacture of polyurethane foam, may cause occupational asthma in susceptible individuals at very low concentrations; in higher concentrations, such as may occur with accidental spillage, it causes a transient flulike illness associated with airflow obstruction. Prompt recognition of this syndrome has led to modifications in the industrial process involved.

Although the acute effects of exposure to many of these gases and vapours are well-documented, there is less certainty about the long-term effects of repeated low-level exposures over a long period of time. This is particularly the case when the question of whether work in a generally dusty environment has contributed to the development of chronic bronchitis or later emphysema—in other words, whether such nonspecific exposures increase the risk of these diseases in cigarette smokers.

Many chemicals can damage the lung in high concentration: these include oxides of nitrogen, ammonia, chlorine, oxides of sulfur, ozone, gasoline vapour, and benzene. In industrial accidents, such as occurred in 1985 in Bhopal, India, and in 1976 in Seveso, near Milan, people in the neighbourhood of chemical plants were acutely exposed to lethal concentrations of these or other chemicals. The custom of transporting dangerous chemicals by rail or road has led to the occasional exposure of bystanders to toxic concentrations of gases and fumes. Although in many cases recovery may be complete, it seems clear that long-term damage may occur.

 

Disability and attribution of occupational lung diseases

virus 5

virus 5

Classification

Distinguishing taxonomic features

Viruses are classified on the basis of their nucleic acid content, their size, the shape of their protein capsid, and the presence of a surrounding lipoprotein envelope.

The primary taxonomic division is into two classes based on nucleic acid content: DNA viruses or RNA viruses. The DNA viruses are subdivided into those that contain either double-stranded or single-stranded DNA. The RNA viruses also are divided into those that contain double-stranded or single-stranded RNA. Further subdivision of the RNA viruses is based on whether the RNA genome is segmented or not. If the viruses contain single-stranded RNA as their genetic information, they are divided into positive-strand viruses if the RNA is of messenger sense (directly translatable into proteins) or negative-strand viruses if the RNA must be transcribed by a polymerase into mRNA.

All viruses falling into one of these nucleic acid classifications are further subdivided on the basis of whether the nucleocapsid (protein coat and enclosed nucleic acid) assumes a rodlike or a polygonal (usually icosahedral) shape. The icosahedral viruses are further subdivided into families based on the number of capsomeres making up the capsids. Finally, all viruses fall into two classes depending on whether the nucleocapsid is surrounded by a lipoprotein envelope.

Some virologists adhere to a division of viruses into those that infect bacteria, plants, or animals; these classifications have some validity, particularly for the unique bacterial viruses with tails, but there is otherwise so much overlap that taxonomy based on hosts seems unworkable. Classification based on diseases caused by viruses also is not tenable, because closely related viruses frequently do not cause the same disease. Eventually, it is likely that the classification of viruses will be based on their nucleotide sequences and their mode of replication, rather than on structural components, as is now the case.

The basic taxonomic group is called a family, designated by the suffix -viridae. The major taxonomic disagreement among virologists is whether to segregate viruses within a family into a specific genus and further subdivide them into species names. Most virologists believe that a binomial nomenclature, as used for bacteria, into italicized and Latinized genera and species is unwarranted. For this reason, no Latin names are used in the classification of viruses presented here. Moreover, only the well-characterized viruses of animals are presented.

 

Robert R. Wagner
Robert M. Krug

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Respiratory disease 4

Allergic lung diseases

There are at least three reasons why the lungs are particularly liable to be involved in allergic responses. First, the lungs are exposed to the outside environment, and, hence, particles of foreign substances such as pollen may be deposited directly in the lungs; second, the walls of the bronchial tree contain smooth muscle that is very likely to be stimulated to contract if histamine is released by cells affected by the allergic reaction; and, third, the lung contains a very large vascular bed, which may be involved in any general inflammatory response. It is therefore not surprising to find that sensitivity phenomena are common and represent an important aspect of pulmonary disease as a whole. The most common and most important of these is asthma.

 

Asthma

Asthma is characterized by spasmotic contraction of the smooth muscle of the airways, by increased production of an abnormally viscous mucus by bronchial mucous glands, and, in severe attacks, by airway obstruction from mucus that has accumulated in the bronchial tree. This results in a greater or lesser degree of difficulty in breathing. One approach to classifying asthma differentiates cases that occur with an identifiable antigen, in which antigens affect tissue cells sensitized by a specific antibody, and cases that occur without an identifiable antigen or specific antibody. The former condition is known as extrinsic asthma and the latter as intrinsic asthma. Extrinsic asthma commonly manifests first in childhood because the subject inherits an atopic characteristic: the serum contains specific antigens to pollens, mold spores, animal proteins of different kinds, and substances from a variety of insects, particularly cockroaches and mites that occur in house dust. Exacerbation of extrinsic asthma is precipitated by contact with any of the substances to which sensitization has occurred; airway obstruction is often worse in the early hours of the morning. The other form of asthma, intrinsic, may develop at any age, and there may be no evidence of specific antigens. Persons with intrinsic asthma experience attacks of airway obstruction unrelated to seasonal changes, although it seems likely that the airway obstruction may be triggered by infections, which are assumed to be viral in many cases. Asthma attacks may be precipitated by food. For example, in small children, sensitivity to milk may stimulate an attack, and, in some adults, sensitivity to sulfite compounds found in some foods and wine may stimulate an attack. A subgroup of asthmatics are so sensitive to aspirin (acetylsalicylic acid) that ingestion of this chemical may lead to a life-threatening attack.

In some people, asthma is acquired as the result of occupational exposure (a special form of intrinsic asthma). Exposure to solder resin used in the electronics industry, to toluene diisocyanate (used in many processes as a solvent), to the dust of the western red cedar (in which plicatic acid is the responsible agent), and to many other substances can initiate an asthmatic state, with profound airflow obstruction developing when the subject is challenged by the agent.

Individuals affected by any type of asthma may exhibit airflow obstruction when given aerosols of histamine or methylcholine at much lower concentrations than provoke airflow obstruction in healthy people. Individuals with asthma may also develop airflow obstruction while breathing cold air or when exercising. These characteristics are used in the laboratory setting to study the airway status of patients.

The severe acute asthmatic attack is characterized by acute difficulty in breathing in which mucus clogs the air passages in such a way that air can be inspired but not expired. Despite the severe respiratory difficulty, the patient remains fully conscious. The most dangerous form of the condition is known as status asthmaticus. The bronchial spasm worsens over several hours or over the course of an entire day, during which the bronchi become plugged with thick mucus and airflow is progressively more obstructed. The affected person becomes fatigued, arterial oxygen tension falls, and carbon dioxide accumulates in the blood (leading to drowsiness). As a result, the acidity of the arterial blood increases to dangerous levels that could lead to cardiac arrest. Prompt treatment with intravenous corticosteroids and bronchodilators is usually sufficient to relieve the attack, but in some cases ventilatory assistance is required. In a few cases, death from asthma is remarkably rapid. The exact mechanism of death in these cases is not completely understood.

Asthma may interrupt normal activities and schooling and provide intense or sustained anxiety, especially in individuals who have experienced one or more severe attacks. It tends to diminish in severity with age, and people who had quite severe asthma in childhood may lead normal lives after the age of 20.

Developed countries around the world are reporting a disturbing increase in the prevalence, severity, and mortality of asthma. For example, today more than 7 percent of children and about 9 percent of adults in the United States suffer from asthma. The reason for this increase is not known; however, evidence points to greater control of ordinary infections during early childhood than was achievable in the 1960s and '70s. For example, children who regularly attend day care or preschool programs acquire more respiratory infections but are less likely to develop asthma later in life. It is possible that frequent infections in early childhood are necessary to “prime” the developing immune system in a way that protects against subsequent development of asthma.

 

Hay fever

Hay fever is a common seasonal condition caused by allergy to grasses and pollens. It is frequently familial, and the sensitivity is often to ragweed pollen. Conjunctival infection and edema of the nasal mucosa lead to attacks of sneezing. Allergic inflammation and the development of polyps in the nasal passages represent a severer form of hay fever that is often associated with asthma.

 

Hypersensitivity pneumonitis

Hypersensitivity pneumonitis is an important group of conditions in which the lung is sensitized by contact with a variety of agents and in which the response to reexposure consists of an acute pneumonitis, with inflammation of the smaller bronchioles, alveolar wall edema, and a greater or lesser degree of airflow obstruction due to smooth muscle contraction. In more chronic forms of the condition, granulomas, or aggregations of giant cells, may be found in the lung. Inflammation can lead to widespread lung fibrosis and chronic respiratory impairment.

One of these illnesses is the so-called farmer's lung, caused by the inhalation of spores from moldy hay (thermophilic Actinomyces). This causes an acute febrile illness with a characteristically fine opacification (clouding, or becoming opaque) in the basal regions of the lung on the chest radiograph. Airflow obstruction in small airways is present, and there may be measurable interference with diffusion of gases across the alveolar wall. If untreated, the condition may become chronic, with shortness of breath persisting after the radiographic changes have disappeared. Farmer's lung is common in Wisconsin, on the eastern seaboard of Canada, in the west of England, and in France. Education of farmers and their families and the wearing of a simple mask can completely prevent the condition.

A similar group of diseases occurs in those with close contact with birds. Variously known as pigeon breeder's lung or bird fancier's lung, these represent different kinds of allergic responses to proteins from birds, particularly proteins contained in the excreta of pigeons, budgerigars (parakeets), and canaries.

An acute hypersensitivity pneumonitis may also occur in those cultivating mushrooms (particularly where this is done below ground), after exposure to redwood sawdust, or in response to a variety of other agents. An influenza-like illness resulting from exposure to molds growing in humidifier systems in office buildings (“humidifier fever”) has been well documented. It is occasionally attributable to Aspergillus, but sometimes the precise agent cannot be identified. The disease may present as an atypical nonbacterial pneumonia and may be labeled a viral pneumonia if careful inquiry about possible contacts with known agents is not made.

 

Acute diseases of the bronchi

Acute bronchitis

Acute bronchitis most commonly occurs as a consequence of viral infection. It may also be precipitated by acute exposure to irritant gases, such as ammonia, chlorine, or sulfur dioxide. In people with chronic bronchitis—a common condition in cigarette smokers—exacerbations of infection are common. The bronchial tree in acute bronchitis is reddened and congested, and minor blood streaking of the sputum may occur. Most cases of acute bronchitis resolve over a few days, and the mucosa repairs itself.

 

Bronchiolitis

Bronchiolitis refers to inflammation of the small airways. Bronchiolitis probably occurs to some extent in acute viral disorders, particularly in children between the ages of one and two years, and particularly in infections with respiratory syncytial virus. In some cases the inflammation may be severe enough to threaten life, but it normally clears spontaneously, with complete healing in all but a very small percentage of cases. In adults, acute bronchiolitis of this kind is not a well-recognized clinical syndrome, though there is little doubt that in most patients with chronic bronchitis, acute exacerbations of infection are associated with further damage to small airways. In isolated cases, an acute bronchiolitis is followed by a chronic obliterative condition, or this may develop slowly over time. This pattern of occurrence has only recently been recognized. In addition to patients acutely exposed to gases, in whom such a syndrome may follow the acute exposure, patients with rheumatoid arthritis may develop a slowly progressive obliterative bronchiolitis that may prove fatal. An obliterative bronchiolitis may appear after bone marrow replacement for leukemia and may cause shortness of breath and disability.

Exposure to oxides of nitrogen, which may occur from inhaling gas in silos, when welding in enclosed spaces such as boilers, after blasting underground, or in fires involving plastic materials, is characteristically not followed by acute symptoms. These develop some hours later, when the victim develops a short cough and progressive shortness of breath. A chest radiograph shows patchy inflammatory change, and the lesion is an acute bronchiolitis. Symptomatic recovery may mask incomplete resolution of the inflammation.

An inflammation around the small airways, known as a respiratory bronchiolitis, is believed to be the earliest change that occurs in the lung in cigarette smokers, although it does not lead to symptoms of disease at that stage. The inflammation is probably reversible if smoking is discontinued. It is not known whether those who develop this change (after possibly only a few years of smoking) are or are not at special risk of developing the long-term changes of chronic bronchitis and emphysema.

 

Bronchiectasis

Bronchiectasis is believed to usually begin in childhood, possibly after a severe attack of pneumonia. It consists of a dilatation of major bronchi. The bronchi become chronically infected, and excess sputum production and episodes of chest infection are common. In some cases, clubbing (swelling of the fingertips and, occasionally, of the toes) may occur. The disease may also develop as a consequence of airway obstruction or of undetected (and therefore untreated) aspiration into the airway of small foreign bodies, such as parts of plastic toys.

Bronchiectasis may also develop as a consequence of inherited conditions, of which the most important is the familial disease cystic fibrosis. Cystic fibrosis is due to the production of an abnormal protein called cystic fibrosis transmembrane conductance regulator, or CFTR. This protein normally serves as a channel for the transport of chloride into and out of cells and regulates the activity of other transport channels, including sodium channels. Defects in the transport of chloride, sodium, and other ions result in unusually high levels of ions inside the cells of the lungs. Thus, fluids are absorbed into the cells from the airways, causing the airways to become dehydrated and impairing the ability of the lungs to clear foreign materials and debris. The most important consequence of cystic fibrosis, apart from the malnutrition it causes, is the development of chronic pulmonary changes, with repetitive infections and bronchiectasis as characteristic features. This condition does not progress to pulmonary emphysema but rather causes obliteration and fibrosis of small airways and dilation and infection of the larger bronchi. Thick, viscid secretions in the bronchial tree are difficult to expectorate.

Management of the condition includes antibiotics to fight lung infections, medications to dilate the airways and to relieve pain, enzyme therapy to thin the mucus, and postural drainage and percussion to loosen mucus in the lungs so it can be expelled through coughing. These therapies, in addition to others, have helped control pulmonary infections and have markedly improved survival in affected persons, many of whom, who would formerly have died in childhood, now reach adult life.

 

Chronic obstructive pulmonary disease

Respiratory disease 5

Chronic obstructive pulmonary diseas

Chronic obstructive pulmonary disease (COPD) refers broadly to a group of conditions that cause irreversible respiratory impairment by increasing obstruction to airflow through the bronchi of the lungs. This condition occurs most commonly in current or former regular cigarette smokers and is present in moderate to severe form in 80 million people worldwide. In 2005 the World Health Organization reported that 5 percent of all deaths around the world were due to COPD.

COPD typically has two components which may be present to varying degrees: chronic obstructive bronchitis and pulmonary emphysema. Individuals who predominantly have emphysema experience symptoms that differ in detail from those who predominantly have chronic bronchitis; however, both disorders contribute to shortness of breath during exercise and to general disability.

 

Chronic bronchitis

The chronic cough and sputum production of chronic bronchitis were once dismissed as nothing more than “smoker's cough,” without serious implications. But the striking increase in mortality from chronic bronchitis and emphysema that occurred after World War II in all Western countries indicated that the long-term consequences of chronic bronchitis could be serious. This common condition is characteristically produced by cigarette smoking. After about 15 years of smoking, significant quantities of mucus are coughed up in the morning, due to an increase in size and number of mucous glands lining the large airways. The increase in mucous cells and the development of chronic bronchitis may be enhanced by breathing polluted air (particularly in areas of uncontrolled coal burning). The changes are not confined to large airways, though these produce the dominant symptom of chronic sputum production. Changes in smaller bronchioles lead to obliteration and inflammation around their walls. All these changes together, if severe enough, can lead to disturbances in the distribution of ventilation and perfusion in the lung, causing a fall in arterial oxygen tension and a rise in carbon dioxide tension. By the time this occurs, the ventilatory ability of the patient, as measured by the velocity of a single forced expiration, is severely compromised; in a cigarette smoker, ventilatory ability has usually been declining rapidly for some years. It is not clear what determines the severity of these changes. Some people can smoke for decades without evidence of significant airway changes, whereas others may experience severe respiratory compromise after 15 years or less of exposure.

 

Pulmonary emphysema

This irreversible disease consists of destruction of alveolar walls. It occurs in two forms, centrilobular emphysema, in which the destruction begins at the centre of the lobule, and panlobular (or panacinar) emphysema, in which alveolar destruction occurs in all alveoli within the lobule simultaneously. In advanced cases of either type, this distinction can be difficult to make. Centrilobular emphysema is the form most commonly seen in cigarette smokers, and some observers believe it is confined to smokers. It is more common in the upper lobes of the lung (for unknown reasons). By the time the disease has developed, some impairment of ventilatory ability has probably occurred. Panacinar emphysema may also occur in smokers, but it is the type of emphysema characteristically found in the lower lobes of patients with a deficiency in the antiproteolytic enzyme known as alpha-1 antitrypsin. Like centrilobular emphysema, panacinar emphysema causes ventilatory limitation and eventually blood gas changes. Other types of emphysema, of less importance than the two major varieties, may develop along the dividing walls of the lung (septal emphysema) or in association with scars from other lesions.

A major step forward in understanding the development of emphysema followed the identification, in Sweden, of families with an inherited deficiency of alpha-1 antitrypsin, an enzyme essential for lung integrity. Members of affected families who smoked cigarettes commonly developed panacinar emphysema in the lower lobes, unassociated with chronic bronchitis but leading to ventilatory impairment and disability. Intense investigation of this major clue led to the “protease-antiprotease” theory of emphysema. It is postulated that cigarette smoking either increases the concentration of protease enzymes released in the lung (probably from white blood cells) or impairs the lung's defenses against these enzymes or both. Although many details of the essential biochemical steps at the cellular level remain to be clarified, this represents a major step forward in understanding a disease whose genesis was once ascribed to overinflation of the lung (like overdistending a bicycle tire).

Chronic bronchitis and emphysema are distinct processes. Both may follow cigarette smoking, however, and they commonly occur together, so determination of the extent of each during life is not easy. In general, significant emphysema is more likely if ventilatory impairment is constant, gas transfer in the lung (usually measured with carbon monoxide) is reduced, and the lung volumes are abnormal. Development of high-resolution computerized tomography has greatly improved the accuracy of detection of emphysema. Some people with emphysema suffer severe incapacity before the age of 60; thus, emphysema is not a disease of the elderly only. An accurate diagnosis can be made from pulmonary function tests, careful radiological examination, and a detailed history. The physical examination of the chest reveals evidence of airflow obstruction and overinflation of the lung, but the extent of lung destruction cannot be reliably gauged from these signs, and therefore laboratory tests are required. (For more information about the methods of detection of lung diseases, see above Methods of investigation.)

The prime symptom of emphysema, which is always accompanied by a loss of elasticity of the lung, is shortness of breath, initially on exercise only, and associated with loss of normal ventilatory ability and increased obstruction to expiratory airflow. The expiratory airflow from a maximum inspiration is measured by the “forced expiratory volume in one second,” or FEV1, and is a predictor of survival of emphysema. Chronic hypoxemia (lowered oxygen tension) often occurs in severe emphysema and leads to the development of increased blood pressure in the pulmonary circulation, which in turn leads to failure of the right ventricle of the heart. The symptoms and signs of right ventricular failure include swelling of the ankles (edema) and engorgement of the neck veins. These are portents of advanced lung disease in this condition. The hypoxemia may also lead to an increase in total hemoglobin content and in the number of circulating red blood cells, as well as to psychological depression, irritability, loss of appetite, and loss of weight. Thus, the advanced syndrome of chronic obstructive lung disease may cause such shortness of breath that the afflicted person has difficulty walking, talking, and dressing, as well as numerous other symptoms.

The slight fall in ventilation that normally accompanies sleep may exacerbate the failure of lung function in chronic obstructive lung disease, leading to a further fall in arterial oxygen tension and an increase in pulmonary arterial pressure.

Unusual forms of emphysema also occur. In one form the disease appears to be unilateral, involving one lung only and causing few symptoms. Unilateral emphysema is believed to result from a severe bronchiolitis in childhood that prevented normal maturation of the lung on that side. “Congenital lobar emphysema” of infants is usually a misnomer, since there is no alveolar destruction. It is most commonly caused by overinflation of a lung lobe due to developmental malformation of cartilage in the wall of the major bronchus. Such lobes may have to be surgically removed to relieve the condition. Bullous emphysema can occur in one or both lungs and is characterized by the presence of one or several abnormally large air spaces surrounded by relatively normal lung tissue. This disease most commonly occurs between the ages of 15 and 30 and usually is not recognized until a bullous air space leaks into the pleural space, causing a pneumothorax.

 

Lung cancer

Up to the time of World War II, cancer of the lung was a relatively rare condition. The increase in its incidence in Europe after World War II was at first ascribed to better diagnostic methods, but by 1956 it had become clear that the rate of increase was too great to be accounted for in this way. At that time the first epidemiological studies began to indicate that a long history of cigarette smoking was associated with a great increase in risk of death from lung cancer. By 1965 cancer of the lung and bronchus accounted for 43 percent of all cancers in the United States in men, an incidence nearly three times greater than that of the second most common cancer (of the prostate gland) in men, which accounted for 16.7 percent of cancers. In 1964 Smoking and Health: Report of the Advisory Committee to the Surgeon General of the Public Health Service (United States) concluded categorically that cigarette smoking is causally related to lung cancer in men. Since then, many further studies in diverse countries have confirmed this conclusion.

The incidence of lung cancer in women began to rise in 1960 and continued rising through the mid-1980s. This is believed to be explained by the later development of heavy cigarette smoking in women compared with men, since women greatly increased their cigarette consumption during World War II. By 1988 there was evidence suggesting that the peak incidence of lung cancer due to cigarette smoking in men may have been passed. The incidence of lung cancer mortality in women, however, is increasing.

The reason for the carcinogenicity of tobacco smoke is not known. Tobacco smoke contains more than 60 carcinogenic compounds, including harmful nitrosamines and polycyclic aromatic hydrocarbons. In addition to its single-agent effects, cigarette smoking greatly potentiates the cancer-causing proclivity of asbestos fibres, increases the risk of lung cancer due to inhalation of radon daughters (products of the radioactive decay of radon gas), and possibly also increases the risk of lung cancer due to arsenic exposure. People who do not smoke but who live or work with smokers and who therefore are exposed to secondhand tobacco smoke have an increased risk for lung cancer.

Because lung cancer is characterized by different types of tumours, because it may be located in different parts of the lung, and because it may spread beyond the lungs at an early stage, the first symptoms noted by the patient vary. These symptoms may include a persistent cough, blood staining of the sputum, a pneumonia that does not resolve fully with antibiotics, or shortness of breath due to a pleural effusion. A physician may discover distant metastases in bone tissues or in the brain that cause symptoms unrelated to the lung. Lymph nodes may be involved early, and enlargement of the lymph nodes in the neck may lead to a chest examination and the discovery of a tumour. In some cases a small tumour metastasis in the skin, abnormal mental function or behaviour, jaundice from liver dysfunction, or sensory changes in the legs from peripheral neuropathy (damage to nerves outside the central nervous system) may be the first sign of the disease. In other cases, only a general feeling of malaise, unusual fatigue, or seemingly minor symptoms may serve as the first indication. In addition, some affected individuals experience clubbing (swelling) of the fingers and toes, an unusual sign that may disappear after surgical removal of the tumour. Lung cancer may develop in an individual who already has chronic bronchitis and who therefore has had a cough for many years.The diagnosis often depends on securing tissue for histological examination, although in some cases this entails removal of the entire neoplasm before a definitive diagnosis can be made.

Survival from lung cancer has improved only slightly since the mid-1970s, when the U.S. government greatly increased funding for cancer research in an effort to find a cure for the disease. Early detection with routine chest radiographs has been attempted, and large-scale trials of routine sputum examination for the detection of malignant cells have been conducted, but neither screening method has been shown thus far to affect long-term mortality. Attention has been turned to prevention by every means possible. Foremost among them are efforts to inform the public of the risk and to limit the advertising of cigarettes. Steps have been taken to reduce asbestos exposure, both in the workplace and in public and private buildings, and to control air pollution. The magnitude of the contribution of air pollution to the incidence of lung cancer is not known with certainty.

Persons exposed to radon are at risk for lung cancer. The hazard from exposure was formerly thought to be confined to uranium miners, who, by virtue of their work underground, encounter high levels of these radioactive materials. However, significant levels of radon have been detected in houses built over natural sources, and, with increasingly efficient insulation of houses, radon may reach concentrations high enough to place the occupants at risk for lung cancer. Major regional variations in the natural distribution of radon occur, and it is not yet possible to quantify precisely the actual magnitude of the risk. In some regions of the world (such as the Salzburg region of Austria), levels are high enough that radon exposure is believed to account for the majority of cases of lung cancer in nonsmokers.

Workers exposed to arsenic in metal-smelting operations, and the community around the factories from which arsenic is emitted, have an increased risk for lung cancer. Arsenic is widely used in the electronics industry in the manufacture of various products, including microchips and semiconductors, and careful surveillance of this industry has helped prevent future disease.

Some types of lung cancer are unrelated to cigarette smoking. Alveolar cell cancer is a slowly spreading condition that affects men and women in equal proportion and is not related to cigarette smoking. Pulmonary adenocarcinoma of the lung also has a more equal sex incidence than other types; although its incidence is increased in smokers, it may also be caused by other factors.

It is common to feel intuitively that one should be able to apportion cases of lung cancer among discrete causes, on a percentage basis. But in multifactorial disease, this is not possible. Although the incidence of lung cancer would probably be far lower without cigarette smoking, the contribution of neither this factor nor any of the other factors mentioned can be precisely quantified. Treatment of most forms of lung cancer may involve chemotherapy, radiation therapy, or surgery (see Lung cancer: Treatment).

 

Occupational lung disease

Respiratory disease 3

Diseases of the mediastinum and diaphragm

The mediastinum comprises the fibrous membrane in the centre of the thoracic cavity, together with the many important structures situated within it. Enlargement of lymph glands in this region is common, particularly in the presence of lung tumours or as part of a generalized enlargement of lymphatic tissue in disease. Primary tumours of mediastinal structures may arise from the thymus gland or the lower part of the thyroid gland; noninvasive cysts of different kinds are also found in the mediastinum.

The diaphragm may be incompletely formed, leading to herniation of abdominal viscera through it. In adult life an important disease involving the diaphragm is bilateral diaphragmatic paralysis. This leads to a severe reduction in vital capacity, especially when the subject is recumbent. In many cases the cause of the paralysis cannot be determined. Paralysis of the diaphragm on one side is more common and better tolerated than bilateral paralysis, although some shortness of breath on exertion is often present. The function of the diaphragm may be compromised when the lung is highly overinflated, as occurs in emphysema; diaphragmatic fatigue may limit the exercise capability of affected persons.

Although these divisions provide a general outline of the ways in which diseases may affect the lung, they are by no means rigid. It is common for more than one part of the system to be involved in any particular disease process, and disease in one region frequently leads to involvement of other parts.

 

Major diseases of the respiratory system

Viral infections of the respiratory system

A wide variety of viruses are responsible for acute respiratory disease. The common cold—frequently of viral origin—can cause inflammation of the trachea and laryngitis, and such inflammation may extend to involve the lower bronchial tree. After such episodes the ciliary lining of the bronchial tree may be damaged, but the repair process is usually rapid.

Infections with rhinoviruses and adenoviruses are especially important in children, in whom they cause a febrile (fever-associated) illness, occasionally with severe bronchiolar involvement. Although recovery is usually rapid, in some infections with respiratory syncytial virus an extensive bronchiolitis develops that may be severe enough to threaten life. In epidemics of these diseases, occasional cases occur in which the course is complicated by inflammation of the pericardium—the membrane enclosing the heart—or by a pleural effusion.

Influenza and parainfluenza viruses are capable of causing severe illness. The influenza virus attacks many systems of the body simultaneously, but the primary site of viral replication appears to be the alveolar cells of the lung. There the virus multiplies many times over within a 24-hour period, and the pulmonary involvement may begin in the parenchyma and cause considerable consolidation and inflammation of lung tissue. Severe tracheitis, bronchitis, and bronchiolitis often occur at the same time. Another form of the disorder is that described as viral pneumonia, in which a distinguishing feature is the presence of patchy areas of atelectasis, or partial collapse of lung tissue, without extensive involvement of the bronchial tree. All these conditions are more dangerous in small children and in the elderly, and the lung that is the seat of a severe attack of influenza may quickly become secondarily infected.

It was secondary bacterial infection that accounted for the high mortality in the influenza epidemic of 1918–19, one of the worst human catastrophes on record. Today this epidemic is more precisely called a pandemic because it affected populations around the world. It has been estimated that more than 20,000,000 people worldwide died during the outbreak; of the 20,000,000 people who suffered from the illness in the United States, approximately 850,000 died. It was a characteristic of this pandemic that young people were severely affected. The high mortality resulted from the lack of antibiotics for treating the secondary bacterial infection; widespread malnutrition probably also contributed to the death rate.

There are three immunologically distinct types of influenza virus, designated A, B, and C; parainfluenza viruses are designated by the letter D. Types A, B, and D cause epidemic disease. Within type A there are known to be at least four distinct strains. The “Asian” strain of type A was responsible for the 1957 influenza epidemic. Epidemic influenza tends to occur in two- or three-year cycles; careful study has allowed predictions to be made of their future occurrence. Although infected individuals develop lasting immunity to a particular strain following an attack of influenza, the immunity is highly specific as to type, and no protection is afforded against even closely related strains. Artificial immunization with high- potency vaccines is of value in protecting against previous strains, and the vaccines have been shown to ameliorate the infection in the general population. Their use is particularly indicated in elderly people whose cardiac or lung function is already compromised.

Psittacosis and ornithosis, primarily infections of birds and particularly common among parakeets and parrots, are transmitted to human beings by inhalation of dust particles from the droppings of infected birds. The onset of psittacosis may be quite severe, with headache, insomnia, and even delirium. Gastrointestinal symptoms such as vomiting and pain are frequent, and a cough productive of clear sputum usually develops after a few days. Mild attacks are often unrecognized and dismissed as due to influenza. Recovery is usually complete, but convalescence may be slow. A pandemic of this disease in 1929 was caused by the shipment of 5,000 parrots into Argentina from Brazil for auction. Many of the birds died, and there was considerable human mortality. Mandatory isolation of imported birds for observation has largely controlled this disease in many countries around the world.

Chickenpox (varicella), particularly when it occurs in adults, may affect the lung. Acute lesions may occur in the lung parenchyma, leading to a transient but significant fall in arterial oxygen tension (hypoxemia), occasionally necessitating oxygen therapy. Recovery may be slow but is usually complete, although shadows may remain on a chest radiograph as a result of it.

Whooping cough occurs in epidemic form among children and appears to be linked to the later development of the chronic infective process known as bronchiectasis, which occurs as a result of bronchial damage. In Western countries, both whooping cough and measles (which causes an acute bronchiolitis) have been largely controlled by effective vaccines, although whooping cough sometimes occurs in adults many years after vaccination. In some developing countries, where these vaccines are not consistently available, whooping cough and measles can still be major causes of mortality in children. Mortality is worsened by malnutrition, which reduces resistance to acute respiratory diseases and is present in many children of developing countries.

The reparative processes in the lung after any viral attack may be quite slow. Apparent clinical recovery may occur relatively quickly and radiographs may show no remaining shadows, yet repair and restitution of the alveolar wall may take several additional weeks. Sometimes a cough persists for two or three months after systemic symptoms have resolved, reflecting continued healing of the bronchi. However, the occurrence of a severe viral infection in childhood may impair subsequent development of the lung or even set the stage for chronic respiratory disease in later life.

 

Bacterial infections of the respiratory system

Pneumonia

Before effective antibiotics became available, pneumonia was the respiratory disease responsible for the greatest mortality and consequently was one of the most-feared diseases. Because it frequently led to the death of severely disabled elderly people, it was also known as the “old man's friend.” The most common form of the disease, streptococcal pneumonia (sometimes called pneumococcal pneumonia), is caused by a streptococcus called Streptococcus pneumoniae. This form of pneumonia begins abruptly with a high fever and severe malaise followed by natural resolution in survivors after several days or longer. In some cases, infection is followed by complications, such as a lung abscess, pleurisy, or heart failure. Prompt antibiotic therapy controls the acute process within 24 hours in most instances; however, some deaths occur despite appropriate antibiotic therapy. Emergence of antibiotic-resistant S. pneumoniae strains is a growing concern. Streptococcal pneumonia may also occur as a complication of an acute attack of influenza because susceptibility to infection by streptococci is increased. In addition, the much-lowered mortality of influenza can be explained by antibiotics effective against streptococci. Staphylococcal pneumonia occurs as an acute illness in small children and may lead to rapid destruction of lung tissue with abscess formation; however, if the acute state is survived, as it usually is with chemotherapy, the lung recovers fully. This type of pneumonia may also occur as a complication of preexisting lung disease of any kind and may follow aspiration of stomach contents into the lung. The development of antibiotic-resistant staphylococci, such as methicillin-resistant Staphylococcus aureus (MRSA), has meant that this form of pneumonia may be a problem in the hospital environment, complicating other lung diseases or occurring postoperatively.

Pneumonia due to infection with Klebsiella pneumoniae may be difficult to treat and characteristically may occur as a repetitive series of episodes of pneumonia, each running a rather long course with slow resolution.

The organism Hemophilus influenzae is commonly isolated from the sputum of patients with chronic bronchitis during acute exacerbations of infection and is an important cause of pneumonia in adults.

Mycoplasma, identified in 1944 as responsible for a group of pneumonias previously thought to be of viral origin, is a member of a group of organisms known as the pleuropneumonia-like organisms and has also been termed the “Eaton agent” after the scientist who first described it. Mycoplasma pneumoniae is the single most common cause of pneumonia in school-age children and young adults. The infection produces soft patchy shadows on the chest radiograph and relatively few signs on physical examination. A nonproductive cough and a fever occur for a few days. Familial spread is common, and disease occurs in epidemic form in young healthy people brought together in clusters, as in military recruit camps and colleges, where a number of outbreaks have been documented. It is not usually a life-threatening disease, but in rare cases it may progress to cause acute respiratory distress syndrome.

In all these bacterial pneumonias, the diagnosis may be made from the characteristic radiographic pattern, together with isolation from the sputum of the bacterium primarily responsible.

 

Legionnaires disease

In July 1976 an outbreak of severe pneumonia occurred among U.S. veterans attending a convention of the American Legion in Philadelphia. Of the 147 persons admitted to hospitals, 29 died. Identification of the organism responsible (subsequently named Legionella pneumophila) constituted a classic medical detective story. The bacterium had evaded detection before because it does not stain with the usual stains used in sputum examination. Today it is known that this bacterium may grow in air-conditioning systems or on shower heads, and it has been shown to be responsible for sporadic but severe outbreaks of pneumonia, particularly but not exclusively in older people. Fortunately, the bacterium is sensitive to erythromycin and other antibiotics.

 

Pneumonia in immunocompromised persons

For some years prior to 1980, it had been known that if the immune system was compromised by immunosuppressive drugs (given, for example, before organ transplantation to reduce the rate of rejection), the patient was at risk for developing pneumonia from organisms or viruses not normally pathogenic. Patients with AIDS may develop pneumonia from cytomegalovirus or Pneumocystis infections, capable of causing invasive pneumonic lesions in the setting of reduced immunity. Such infections are a major cause of illness in these patients, are difficult to treat, and may prove fatal. Infections with fungi such as Candida also occur. The diagnosis and management of these cases has become a challenging and time-consuming responsibility for respiratory specialists in locations with large numbers of AIDS cases.

 

Tuberculosis

Of all the lung diseases caused by bacteria, pulmonary tuberculosis is historically by far the most important. Particular features of this dreaded condition include the severe general debilitation and weakness that it may cause; the insidious nature of the onset of its initial symptoms, which may not be pulmonary in nature; the familial tendency; the long-drawn-out course of the disease and the distressing nature of many of its manifestations, particularly severe hemorrhage from the lung and from tuberculous involvement of the brain (meningitis), or involvement of the adrenal gland leading to adrenal insufficiency (Addison disease); and, above all, the general inefficacy of medical treatment before effective antibiotic therapy became available. Antibiotics have greatly reduced the mortality from pulmonary tuberculosis in all developed countries, but the decline in mortality began well before their introduction, and it is clear that improved diet and housing were responsible for this. With antibiotic therapy, however, the bacilli quickly disappear from the sputum and the spread of infection is quickly controlled.

In its classic form, tuberculosis first causes pulmonary inflammation at the apices (upper portions) of the lungs, and it may progress slowly to form a chronic cavity in this region. Secondary infection of the cavity may occur and may be difficult to eradicate. When still active, pulmonary tuberculosis is a constant threat to the patient, because blood-borne spread may occur at any time. Diffuse spread of tuberculosis in the lung (known as miliary tuberculosis) may occur at the onset of the disease. The chest radiograph reveals many small and diffuse shadows. The exact sequence of events that leads to this disseminated form of disease is not understood, but prompt treatment is required to prevent spread to the brain and other organs. Pulmonary tuberculosis remains an important disease.

Treatment of tuberculosis is based on whether an individual has tuberculosis infection or tuberculosis disease. Treatment of the former is aimed at preventing disease and often involves only one drug, whereas treatment of the latter is aimed at fighting the disease and involves regimens that employ multiple drugs. Streptomycin was the first clinically successful antituberculous drug; however, it is only occasionally used today. Most cases of tuberculosis infection are treated with isoniazid (isonicotinic hydrazide). Treatment often lasts for a period of six to nine months. In the case of active tuberculosis disease, the combination of isoniazid, rifampin, pyrazinamide, and ethambutol is often used for a period of six months to a year. There is no one “best” regimen preferable to all others since tubercle bacilli can acquire resistance to most of the antituberculous drugs. The development of resistance to antibiotics is often delayed by the concomitant use of two or more drugs, by continuous treatment without significant interruption until all bacterial growth has ceased, and by the use of bed rest and resectional surgery in a few selected cases. Surgery may be indicated when a chronic cavity has developed.

The major problem in treating pulmonary tuberculosis is ensuring continued medication and supervision. This may be very difficult in developing countries and in isolated regions of the world. Although the death rate from respiratory tuberculosis in the Western world has fallen greatly since 1900, it remains a serious and difficult problem in many tropical countries and in any population with inadequate medical care and poor diet and hygiene. In addition, pulmonary tuberculosis has reappeared in the West in persons with AIDS, in whom treatment is complicated by diminished immunity.

 

Q fever

Q fever is an infection with the pathogenic bacteria Coxiella burnetii. The disease was first described in Queensland, Australia; areas in which Q fever is known to be endemic include Australia, the western United States, Africa, England, and the Mediterranean countries. Animal infection is widespread and involves a large variety of domestic farm animals, particularly cattle and sheep, and some wild animals. Transmission is believed to occur between mammals through ticks and mice. Human disease, which is uncommon, is probably acquired through inhalation of infected material. Laboratory workers and employees in slaughterhouses are particularly at risk. Q fever is usually a mild and self-limited disease, requiring only symptomatic treatment.

 

Allergic lung diseases

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Respiratory disease 2

Lung transplantation

Early attempts at transplanting a single lung in patients with severe bilateral lung disease were not successful, but from the late 1970s bilateral lung transplantation had some striking results. Persons severely disabled by cystic fibrosis, emphysema, sarcoidosis, pulmonary fibrosis, or severe primary pulmonary hypertension can achieve nearly normal lung function several months after the procedure. Because transplantation offers the only hope for persons with severe lung disease, who may be relatively young, the techniques are being pursued aggressively in specialized centres. Availability of donor lungs is sharply limited by the number of suitable donors; for example, many people who die of severe head injuries, which presumably would leave the lungs intact, often have also suffered lung injury or lung infection. With proper selection of donor organs and proper transplantation technique, survival at one year has been reported at 90 percent.

Many recipients of single or double lung transplantation develop bronchiolitis obliterans beginning several months or years after surgery. This complication is thought to represent gradual immunologic rejection of the transplanted tissue despite the use of immunosuppressant drugs. Brochiolitis obliterans and the constant risk of serious infection brought about by the use of immunosuppressant drugs limit survival to approximately 40 to 60 percent five years after surgery.
 

Morphological classification of respiratory disease

The main divisions of the respiratory system serve as a basis for the morphological description of respiratory system diseases. The upper airway consists of the nose, nasopharynx, and larynx. Below these structures lies the trachea. Thereafter the airway divides into two major airways, right and left, and then into progressively smaller tubes until finally the terminal bronchioles, which are about one millimetre in diameter, are reached. On average, 16 generations of division occur between the trachea and the terminal bronchioles. Although there is only one airway at the beginning—the trachea—there are about 650,000 terminal bronchioles. The cross-sectional area of the bronchial tree increases with increasing subdivision. The end of each terminal bronchiole opens into an acinus, so called because the structure resembles a cluster of grapes, and from this point onward the gas-exchanging portion of the lung is reached. The alveoli, or air sacs, which are divided into groups or lobules by fibrous partitions, or septa, are small hexagonal structures forming a blind end to the acinus. The wall of the acinus consists of blood capillaries, and the remaining structures are extremely thin, only providing supporting tissue for the rich capillary bed that constitutes the parenchyma, or the essential tissue of the lung itself. The parenchyma is the gas-exchanging tissue of the lung and has a surface area roughly comparable to that of a tennis court. Blood is distributed to the lung through the branching pulmonary artery, which subdivides with the bronchial tree and accompanies the smaller bronchioles into the region of the acinus to supply the capillaries of the alveolar wall. Oxygenated blood from the acini is collected into pulmonary veins, which run at some little distance from the bronchioles. An interstitial space exists around the alveoli and around the bronchioles and blood vessels, and this connects the lymph nodes (the small masses of lymphatic tissue that occur along the course of the lymph vessels) situated in the midline of the thoracic cavity and extending in a chain up into the neck and down into the abdomen.

Each lung is covered by a protective membrane, or pleura, which consists of a visceral layer that lines the outer surface of the lung and a parietal layer that lines the inside of the chest wall. The space between these two layers, called the intrapleural space, normally contains no air and only a few millilitres of fluid for lubrication purposes, as during breathing one layer must slide on another. The pleurae may become involved by inflammation or neoplastic disease, in which case an effusion of fluid may occur between the two layers.

From this general description, diseases of the respiratory system may be grouped into the following categories.

 
Diseases of the upper airwayThe nasal sinuses are frequently the site of both acute and chronic infections. In common with the palate and the nasopharynx, they are also the site of malignant neoplastic changes. Cancer of the larynx is much more common in smokers than in nonsmokers.

The occurrence of upper airway obstruction (particularly common in people who snore) has been documented in sleep laboratory studies. Sleep apnea, which sometimes involves upper airway obstruction, is characterized by cessation of breathing for up to a minute and by a marked fall in blood oxygen levels, thus arousing an affected individual from sleep. Sleep apnea affects approximately 4 percent of adults. It is not confined to the very obese, although it forms part of the syndrome of severe obesity in which sleep disturbance is common, and it is associated with the daytime somnolence known as the pickwickian syndrome, after Charles Dickens's description of the fat boy in The Pickwick Papers. Sleep apnea is sometimes caused by relaxation of muscles around the pharynx and obstruction of the airway by the palate and tongue. It is related to narrow anatomical dimensions in this area but is also more likely to occur if alcohol is ingested shortly before sleep. Sleep apnea may cause a rise in systemic blood pressure, and pickwickian syndrome may affect one's performance at work and ability to do other tasks carried out during the day. In severe cases, sleep apnea leads to right ventricular heart failure.

 

Diseases of the major bronchi

The major bronchi can become the seat of chronic inflammation, as in chronic bronchitis or bronchiectasis. The latter disease may be caused by the familial disease cystic fibrosis (see below Bronchiectasis). The major bronchi may also be the site of development of malignant disease.

 

Diseases of the smaller bronchi and bronchioles

It is in the smaller bronchi that major obstruction commonly occurs in asthma: these bronchi contain smooth muscle in their walls, and the muscle may contract, causing airway obstruction. The small radicles of the bronchial tree, the bronchioles, are commonly involved in infective processes such as viral infections; they are also the primary site of deposition of inhaled dust and particles. Because of the large cross-sectional area of this part of the airway, considerable disease may be present in the bronchioles without affecting the expiratory flow rate. The bronchioles are occasionally the site of a primary noninfective bronchiolitis in persons with rheumatoid arthritis or other systemic inflammatory diseases.

 

Diseases of the alveolar ducts and alveoli

These structures are the site of primary involvement in many infections, including pneumonia, and it is on the parenchyma of the lung that the main effects of blockage of a pulmonary artery (pulmonary embolism) occur. The capillary bed surrounding the alveoli is subject to damage, and fluid may leak through the alveolar capillaries to accumulate in the lungs (pulmonary edema). The capillary bed is also extensively damaged in the condition known generally as acute respiratory distress syndrome; the exact mechanism of the damage is not yet fully understood. The alveolar walls themselves may undergo diffuse interstitial thickening, a characteristic of diseases grouped under the heading of “diffuse interstitial fibrosis”; interstitial thickening may also occur as a manifestation of collagen diseases such as scleroderma. One of the common forms of emphysema, in which alveolar destruction occurs, entails early loss of tissue at the point where the bronchiole ends in the acinus, resulting in a punched-out lesion in the centriacinar region. This form of emphysema is the one that most commonly develops after years of cigarette smoking.

The lung parenchyma is the site of the discrete aggregations of cells, usually giant cells, that form the granulomas characteristic of the generalized disease known as sarcoidosis, and it is in the lung parenchyma that nodules caused by the inhalation of silica particles are found.

 

Diseases of the pleura

The pleura may be involved in inflammatory or neoplastic processes, either of which may lead to fluid accumulation (pleural effusion) between the two layers. The pleural membranes of the lungs may become perforated and spontaneously rupture, usually over a small collection of congenital blebs, or cysts at the apex of the lung. This causes spontaneous pneumothorax, a partial or occasionally complete collapse of the lung. In the majority of cases, a pneumothorax resolves slowly of its own accord, although pleural suction may be needed to expedite recovery. If repetitive attacks occur, the blebs may be removed surgically, and the pleural membrane of the affected lung may be sealed to the pleural membrane of the inner wall of the thorax to prevent a recurrence.

The most common disease of the pleura is caused by inflammation and is referred to as pleurisy. A pleurisy with an effusion may be the presenting symptom of pulmonary tuberculosis, and pleurisy may accompany any kind of pneumonia. When a pleural effusion in a person with bacterial pneumonia becomes infected, pus accumulates in the pleural cavity (empyema). This complication—dreaded before the widespread availability of antibiotics in the mid-20th century and after the outbreaks of antibiotic-resistant microorganisms in the late 20th and early 21st centuries—requires drainage of the pleural space. In severe instances of empyema, video-assisted thoracic surgery is performed to evacuate viscous or semisolid infected material from the space.

Mesothelioma, a cancer of the pleura, may occur many years after inhalation of asbestos fibres (see below Asbestosis and mesothelioma). The cancerous cells of the pleura can eventually metastasize and invade nearby and distant tissues, including tissues of the neck and head.

Respiratory disease 1

Respiratory disease

Introduction

any of the diseases and disorders that affect human respiration

Diseases of the respiratory system may affect any of the structures and organs that have to do with breathing, including the nasal cavities, the pharynx (or throat), the larynx, the trachea (or windpipe), the bronchi and bronchioles, the tissues of the lungs, and the respiratory muscles of the chest cage.

 

 

• During normal breathing, inhaled air travels through two main channels (primary bronchi) that …

The respiratory tract is the site of an exceptionally large range of disorders for three main reasons: 1) it is exposed to the environment and therefore may be affected by inhaled organisms, dusts, or gases; 2) it possesses a large network of capillaries through which the entire output of the heartblood vessels are likely to affect the lung; and 3) it may be the site of “sensitivity” or allergic phenomena that may profoundly has to pass, which means that diseases that affect the small affect function.

This article discusses the signs and symptoms of respiratory disease, the natural defenses of the human respiratory system, the methods of detecting respiratory disease, and the different diseases of the respiratory system. For more information about the anatomy of the human respiratory system and the process of respiration, see human respiratory system.

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