History

Antiquity Through the Eighteenth Century Lobar pneumonia has probably always afflicted humans. Pneumococcal organisms have been found in prehistoric remains, and evidence of the disease itself has been observed in Egyptian mummies from 1200 B.C. (Ruffier 1921; Janssens 1970; Grmek 1983). Epidemics of this disease are probably less common than has previously been thought, however. In his pre-germ-theory observations, Hirsch cited sixteenth- to late-nineteenth-century reports of epidemic outbreaks of "pneumonia" in numerous places on six continents. He emphasized that nearly all these records drew attention to "the malignant type of disease" and the "typhoid symptoms" (Hirsch 1886). These qualifiers raise doubts about whether or not these outbreaks were truly pneumonia. It is probable that most, if not all, were caused by organisms other than pneumococcus. Conditions now called by another name and known to have pneumonic manifestations, like plague and influenza, are far more likely candidates for retrospective diagnosis (Stout 1980).

Pneumonia is not only an old disease, it is also one of the oldest diagnosed diseases. Hippocratic accounts of a highly lethal illness called peripleu-monin give a readily identifiable description of the symptoms, progression, and suppurative complications of classic pneumonia and localize the disease to the lung. This disease was a paradigmatic example of the Greek theory that held that all illness progressed through coction (approximately, incubation and early illness) to crisis and lysis (breaking up), while certain days in this sequence were "critical" to the outcome (Sigerist 1951). These writers based the diagnosis on the symptoms, but the physical sign of "clubbing" or "Hippocratic nails" was associated with prolonged pneumonia. Auscultation was also recommended to confirm the presence of pus in the chest. Variant pneumonic conditions of the lung were also described, including lethargy, moist and dry pneumonia, also called erysipelas of the lung. Therapy included bleeding, fluids, expectorants, and, only if absolutely necessary, surgical evacuation of empyemic pus (Hippocrates 1988; Potter 1988).

In the first century A.D., Aretaeus of Cappadocia distinguished this disease from pleurisy, and four centuries later Caelius Aurelianus recognized that it could be confined to only certain parts of the lung. Except for a few subtle modifications, little change occurred in the clinical diagnosis and treatment of pneumonia until the early nineteenth century.

Nineteenth Through Twentieth Century

It is true that eighteenth-century pathological anatomists drew attention to the microscopic appearance of the lung in fatal cases of lobar pneumonia. This work, however, had little impact on diagnosis until 1808, when Jean-Nicolas Corvisart translated and revised the 1761 treatise on percussion by Leopold Auenbrugger. This technique made it possible to detect and localize the presence of fluid or consolidation in the lung and to follow its evolution. Eight years later, Corvisart's student, René Laennec, carried this one step further when he invented the stethoscope. In calling his technique "médiate auscultation," Laennec readily gave priority to Hippocrates for having practiced the "immediate" variety by direct application of the ear to the chest. Laennec recommended both percussion and auscultation of the breath sounds and voice to confirm the physical diagnosis of pneumonia. With this combination he was able to distinguish consolidated lung from pleural fluid or pus in the living patient. He introduced most of the technical terms for pathological lung sounds - including "rale," "rhoncus," "crepitation," "bronchophony," "egophony" - some of which became pathognomonic for disease states. In addition, he adopted Giovanni Morgagni's notion of "hepatisation of the lung," as a descriptive term for consolidation. Percussion and auscultation changed the concept of pneumonia from a definition based on classic symptoms to one based on classic physical findings. This conceptual shift was endorsed but not altered by the advent of the chest X-ray at the turn of this century.

The Italians Giovanni Rasori and Giacomo Thom-masini had recommended high-dose antimony potassium tartrate (tartar emetic) as a treatment for pneumonia, and Laennec used the new method of statistical analysis with historical controls to suggest that this was an effective remedy. Yet in spite of its potential utility, the extreme toxicity of the drug guaranteed its unpopularity (Duffin 1985). Benjamin Rush, an American, and Laennec's contemporary, Jean Baptiste Bouillaud, were proponents of copious

"coup sur coup" phlebotomy. Until the late nineteenth century, when salicylates became available for fever, pneumonia therapy consisted of various combinations and quantities of the ancient remedies, emetics, mercury, and especially bleeding (Risse 1986; Warner 1986).

Germ theory had a major impact on the concept of pneumonia, but it was rapidly apparent that despite its fairly homogeneous clinical manifestations this disease was associated not with a single germ (like tuberculosis and cholera) but with a variety of pathogens. This situation cast some doubt on the imputed role of each new pathogen. In December 1880, Louis Pasteur isolated the organism that would later become the pneumococcus. Carl Friedlander discovered the first lung-derived pneumonia organism, K. pneumoniae (Friedlander's bacillus) in 1883. Albert Frankel identified the pneumococcus CD. pneumoniae) in 1884, and Anton Weichselbaum confirmed his findings in 1886. Klebsiella was found to be quite rare and seemed to favor the upper lobes, whereas the pneumococcus favored the lower lobes; however, there was some overlap between the pneumonic states induced by these organisms. Specific diagnoses could be made only by isolation of the pathogen in culture.

Gradually many other organisms and viruses came to be associated with pneumonia, usually in clinical settings that deviated more or less from classic lobar pneumonia. For example (and to name only a few), H. influenzae was isolated in 1918; Mycoplasma pneumoniae (the "Eaton agent" of "atypical pneumonia") in 1944; L, pneumophila in 1977 (Hudson 1979; Denny 1981; Stevens 1981; Levin 1984). It is likely that new pathogens will be recognized as antibiotics and vaccination alter the ecology of the lung.

Knowledge of the pneumococcus led to improvement in treatment and reduction in mortality from pneumonia, but it also had a major impact on the broad fields of immunology, bacteriology, and molecular genetics. Study of the capsule - its antigenic properties and capacity to transform - provided key information about drug resistance in bacteria: Acquired assistance of pneumococci was first recognized in 1912, long before the antibiotic era (Austrian 1981). Rufus Cole, Raymond Dochez, and Oswald Avery developed typologies for the pneumococci before and during World War I, and in 1929 René Dubos discovered a bacterial enzyme that decomposed the capsular polysaccharide of type ni pneumococcus, a discovery that contributed to the later work of Jacques Monod (Benison 1976).

Treatment and prevention of pneumonia have been dramatically improved in the twentieth century. Oxygen therapy was introduced by William C. Stadie during the 1918 New York influenza epidemic (Harvey 1979). Typing of pneumococci led to the 1912 introduction of antisera by Rufus Cole, who claimed that, by 1929, this therapy reduced mortality in some populations to 10.5 percent (Dowling 1973). Antisera were effective only when the exact type of pneumococcus was known. Gerhard Domagk's Pronotosil (sulfanilamide) was not particularly effective against pneumococcus, but it did control other predisposing conditions. Its successor, sulfapyridine, was more effective. The advent of penicillin in the mid-1940s led to further reduction in mortality; however, it also led to the evolution of penicillin-resistant strains of pneumococci and the now seemingly endless chase after effective derivatives against so-called new organisms (Weinstein 1980).

Pneumonia control programs relied at first on antipneumococcal serum therapy, but as early as 1911, Almroth E. Wright conducted vaccination trials on thousands of black South African gold miners (Dowling 1973; Austrian 1981). These trials, conducted before the diversity of capsular types was fully appreciated, were inconclusive. It was not until 1945 that unequivocal demonstration of protection against type-specific pneumococcal infection in humans was demonstrated by Colin M. MacLeod and Michael Heidelberger using a tetravalent vaccine. Contemporary vaccines contain at least 23 capsular antigens and are 80 to 90 percent effective in immunocompetent persons, but may be useless in some forms of immunodeficiency.

Jacalyn Duffin

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