What is pneumonia?

Causes and Symptoms

Although modern medicine succeeded several generations ago in identifying the key viruses and bacteria responsible for pneumonia and in developing efficient medications for its treatment, a surprisingly high number of deaths from the complications of pneumonia continue to occur. In large part this is the case because pneumonia, which involves infection and inflammation in the respiratory system, occurs not only on its own but also as a complication brought about by other serious illnesses. In aged patients, especially, general deterioration of the body’s resistance to bacterial or viral infection can lead in a final stage to death from pneumonia.

Just as the causes of pneumonia can vary, the disease itself may take different forms. Some sources postulate that pneumonia is not a single disease but a group of advanced lung inflammations. Because they are so similar in their symptoms and effects on the body, all members of this family of diseases are labeled as one form or another of pneumonia. Specific forms range from lobar pneumonia (caused by the bacterial invasion of Streptococcus pneumoniae into a single lobe of one lung) and bronchopneumonia (from Haemophilus influenzae bacteria colonizing in the bronchi) to viral pneumonia (which may be caused by complications originating from chickenpox or influenza virus). In all cases, symptoms include painful coughing, but other symptoms, such as high fever, reduced sputum production, or discolored (rust-tinged or greenish) sputum, may differ. It follows that the drugs that have been developed to treat pneumonia necessarily vary according to the variety of the disease involved.

Lobar pneumonia and bronchopneumonia are the two main classes of disease. The former occurs when an initial infection attacks only one lobe of one lung. Bronchopneumonia results from an initial inflammation in the bronchi and bronchioles (air passages to the lungs), which then spreads to the internal tissue of one or both lungs. Once the symptoms of pneumonia have become visible, any of the following may occur: fever, chills, shortness of breath, chest pains, or a painful cough that produces yellow-green or brownish sputum. These symptoms occur because of a condition called
pleurisy, which is an inflammation of the membrane lining the lungs themselves and the general chest cavity area.

Some assumptions about the causes of pneumonia being limited to bacterial or viral sources have been altered. In particular, clinical observation of patients suffering from AIDS reveals that certain fungi, yeasts, or protozoa can cause pneumonia in these and other cases where immunodeficiency disorders are present.

Although it is apparent that pneumococci can thrive in various parts of the bodies of animals, particularly monkeys and humans, the process that leads to general infection and a concentrated and dangerous attack on the pulmonary system has been the subject of many medical investigations. It is nearly certain that the presence of the
common cold virus in the upper respiratory tract can create the conditions needed for the movement of pneumococci from areas of the body where they may be generally present without causing harm (mainly in saliva) into the pulmonary system. Under conditions of normal health, many body mechanisms can stop a potential invasion of the pulmonary system. This process may involve nasal mucus, although it is not itself bactericidal (bacteria-killing), and other mucous membranes in the region of the larynx. Even beyond the larynx and vocal cords, mechanical means associated with the upward sweep of hairlike protrusions called cilia on the inner linings of deeper respiratory
membranes tend to protect the bronchial tree.

When normal protective processes are reduced, as when the cold virus is present, pneumococci may reach the lower respiratory zone and the parenchyma of the lung, where they settle and multiply. The metabolic products that accumulate as a result of this reproductive process begin to have injurious effects on the respiratory organs. Such injuries become actual lesions in the internal respiratory tissues. The process of infection that follows involves the deposition of fibrin in the adjacent blood and lymph vessels. This phenomenon actually tends to shield the invading organisms from the effects normally produced by antipneumococcal immune substances carried by the blood. If unchecked by medical treatment, reproduction of the invading pneumococci can lead to more extensive lesions. If tissue damage occurs, this can cause the formation of edema, a dangerous accumulation of fluids in spaces where fluids are not normally found. At a later stage of the disease, it appears that the pneumococci enter the interstitial and lymphatic tissues. The unchecked advance of pneumonia infection produces a general deterioration of vital breathing processes as excess fluids spread farther into the respiratory
system. In weakened or immunocompromised individuals, this process can lead to death.

Treatment and Therapy

Medical treatment of the two main types of pneumonia is not the same. Lobar pneumonia requires treatment with penicillin. Bronchopneumonia, although also caused by pneumococcus bacteria, must be treated with different
antibiotics. Most forms of pneumonia caused by viral infections, including psittacosis and mycoplasmal pneumonia, require one of two specific drugs: tetracycline or erythromycin. When viral pneumonia provides the basic disease to which bacterial infections in the lungs are added, however, antibiotics represent the main general means of treatment.

Since World War II, the progress of medical science in dealing with various types of pneumonia has been marked by the development of antimicrobial drugs that can be used in treating diagnosed cases of pneumonia. One of the earliest such drugs, which eventually turned out to be ineffective, was a derivative of quinine called Optochin. It was used for the first time on mice in 1912. Five years later, when the drug was applied to human patients, it was observed that the pneumococci were able to develop a surprising degree of resistance to these early antimicrobial substances. Thus, just as progress in the field of immunization had to wait for a later generation, so did effective drugs such as penicillin and other antibiotics that have become standard tools in the treatment of forms of pneumonia.

In most cases, advances in drug treatment to cure pneumonia have been strikingly successful. The phenomenon of the nonbacterial, nonviral version of Pneumocystis pneumonia arrived very soon after these successes. It posed a particular series of dilemmas for medical science in the 1980s and 1990s. This problem emerged when it became apparent that certain drugs that had been developed to treat pneumonia, in particular the drug combination of trimethoprim-sulfamethoxazole (TMP-SMZ), failed to achieve expected results in a rising number of cases of Pneumocystis pneumonia. This particular form of pneumonia turned out to be among the minority strains of the disease caused by single-celled microorganisms called protozoa.

The importance of P. carinii (also called P. jirovecii) in applied medical science soon extended beyond the restricted domain of pneumonia pathology. It had been discovered in 1909 in Brazil and was thought to affect only animals. This research involved local researchers led by the Italian Antonio Carini, whose name was attached to the discovery. It was only much later, in the 1940s and 1950s, that the presence of P. carinii could be traced to pneumonia in human infants. This meant that a relatively unusual form of pneumonia belonged to limited number of cases caused not by bacteria or viruses but by fungi, yeasts, or microorganisms, specifically, single-celled protozoa. This form of pneumonia remained a relatively rare occurrence until the number of AIDS cases increased.

What appeared to be a near epidemic frequency of P. carinii was in fact a marker or indicator for discovering patients suffering from AIDS. This observation made it possible to immediately test for the presence of AIDS whenever cases of P. carinii appeared. Clinical experience during the 1980s revealed that at least 60 percent of all persons suffering from AIDS had contracted or would contract P. carinii pneumonia. The presence of P. carinii is now assumed to be associated with AIDS unless that diagnosis is excluded by a laboratory test.

It is important to note that relatively rapid advances made by medical researchers in preventing the spread of P. carinii and in treating the cases that did occur among infants led to a new appreciation for pneumonia. Applied research dating from 1958 and extending into the 1970s produced surprisingly effective agents to combat P. carinii pneumonia. This work led to the early application of drugs to people infected with Human immunodeficiency virus (HIV). The concept of multiple drug therapy, patterned on TMP-SMZ, was also successfully applied in the field of cancer treatment.

Another drug, pentamidine, had been used to treat P. carinii pneumonia. When TMP-SMZ seemed to provide a superior treatment, pentamidine production was halted. When the potential utility of pentamidine in treating AIDS became apparent, the Centers for Disease Control and the Food and Drug Administration (FDA) had to take special action in 1984 to license an American supplier. This is how pentamidine quickly became widely available to treat individuals with AIDS. Pentamidine has also been successfully used as an effective treatment for a variety of viral diseases.

A side effect of these AIDS-related developments by the mid-1980s has been to reemphasize the importance of pneumonia. This renewed interest involves both treatments that are most appropriate for different types of pneumonia and research that is still needed to understand fully the role of this family of diseases in modern medicine and society.

Perspective and Prospects

Although modern medicine has not been able to reduce substantially or eliminate totally the number of cases of pneumonia, much has been learned about the disease and its causes. Scientific advances in the campaign to combat the effects of pneumonia in all areas of the world began with the first isolation of Streptococcus pneumoniae in France and the United States in 1880. The French discovery of pneumococci is associated with the laboratory of Louis Pasteur. Simultaneously, George Sternberg was completing work in the medical department of the US Army. In the first decade after the isolation of pneumococci, many different researchers contributed to laboratory findings that linked these bacteria to inflammatory infections in the lungs of animals. They extended their research to include the effects on humans.

One of the most important early breakthroughs came in 1884 when the Danish researcher Hans Christian Joachim Gram developed a laboratory method for identifying specific bacteria in tissue specimens. This technique, called Gram’s stain, revealed that different chemical reactions occur when samples of lung tissue and secretions from individuals ill with pneumonia and healthy persons are tested. The tissues stain very differently. The next step would lead to research into the phenomenon of phagocytosis, a process within pulmonary tissue that combats inapparent pneumococcus infection in healthy people. This specific discovery became linked with efforts to develop an immunization technology against pneumonia.

Until the 1980s, medical researchers used their knowledge of pneumonia mainly to develop methods of immunization against the disease. They also tried to diversify the drugs used in treating pneumonia. Efforts to produce a vaccine against pneumonia began with experiments by the German researchers George and Felix Klemperer, who tested antiserum in animals in 1891. The Klemperers were able to show that the offspring of adult rabbits which had been immunized were resistant to pneumococcal invasion and infection. Soon thereafter, they carried out the first injections of immune serum into human patients. This research ultimately led to the finding that there was no actual antitoxin or antibacterial property in the serum. Instead, it promoted phagocytosis, a process of encapsulation around pneumococci that aids in the immunological response of white blood cells in the body. The vaccine stimulates the body to create its own defenses.

In 1911 in South Africa, an experimental pneumonia vaccine program was undertaken. Although the specific program was not successful, the British physician and scientist Frederick Lister extended its theory. Unequivocal success with a pneumonia vaccine did not come until the last year of World War II. In 1945, C. M. MacLeod and several colleagues published research findings proving that pneumococcal infection in humans was preventable through the use of vaccines containing as many as fourteen specific antigens. These were termed capsular polysaccharides. The breakthrough that made those findings possible had been pioneered in 1930 when these antigens were injected into human beings for the first time. Previously, they had been used only in experiments with mice.

Pneumonia vaccines are critically important components of programs to prevent disease among older members of the population. In March 2013, the American Journal of Medicine published a study of 1,400 pneumonia patients over the age of fifty in which researchers found a correlation between pneumonia patients requiring hospitalization and an increased risk of decline their mental abilities. Experts recommend that the elderly receive a pneumonia vaccine each year. The death rate from pneumonia continues to rise, but not as quickly as the percentage of the population that is elderly. Pneumonia is one of the ten leading causes of death in the United States. In 1900, it was the second or third most common killer. Without vaccines, it might easily still be the second or third leading cause of death.

Children under the age of two are also at high risk for catching pneumonia. The World Health Organization reported in April 2013 that pneumonia was the leading cause of death in children worldwide, killing an estimated 1.2 million children younger than five each year. Only about 30 percent of the world's children with the disease receive antibiotics to treat it

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