Acute Diseases: Pneumonia and Influenza

Obtaining figures on the incidence and burden of pneumonia and influenza in adults throughout the developing world has been surprisingly difficult. Much of the research and surveillance has been directed toward the pediatric age group (see chapter 25). In 2000, fatal lower respiratory infections, as a class that represents serious pneumonia and influenza, were reported as the cause of 120 deaths per million men and 76 deaths per million women worldwide for the 15 to 59 age group (WHO 2000). For both sexes in this age group, this statistic represents approximately one-third of the deaths caused by tuberculosis. However, for the age groups over 60, rates of death from lower respiratory disease more than double for each decade of life, whereas rates of death from tuberculosis remain relatively constant. Notably, acute respiratory diseases—in addition to tuberculosis—remain major concerns among adults with AIDS.

The diagnosis of pneumonia varies according to the patient's access to medical care. Often the diagnosis is made simply on the basis of cough and fever. For patients with access to a hospital, the likelihood of obtaining a chest x-ray increases; generally the infection is bacteriologically confirmed only in the most sophisticated medical centers. The natural history of pneumonia without antibiotic treatment varies with the etiologic agent and the patient's underlying comorbid conditions and age. Mortality resulting from these lower respiratory diseases is approximately 10-fold higher in people age 60 to 69 than in people age 15 to 59 (WHO 2000). Comorbid conditions, malnutrition, low socioeconomic status, and cigarette smoking each play a role in increasing the incidence of disease and worsening the prognosis, both with and without treatment.

From studies conducted in the developed world, it would be reasonable to conclude that common antibiotics for pneumonias that occur outside a hospital setting would effectively reduce days lost from work and, in the absence of other morbid conditions, mortality. The few studies in which sputum specimens have been cultured suggest that Streptococcus pneumoniae is found in between 40 and 50 percent of the cases. Gram-negative organisms or mixed infections are often isolated, and thus, the use of broad-spectrum antibiotics is warranted (Hooi, Looi, and Ng 2001; Hui and others 1993; Lieberman and others 1996). As would be expected, increased use of antibiotics has resulted in increased resistance to common antibiotics. In addition, 10 to 15 percent of these cases may be tuberculosis (Dolin, Raviglione, and Kochi 1994).

Scott and others (2000) suggested that, despite the similarity of the mortality rates for hospital-treated pneumonia in developing and developed countries, there are important differences in the age distributions. The median age at death among Kenyan adults was 33 years, in contrast to more than 65 years in more developed countries. Many patients in developing countries present late in the course of the disease. Often they die before an appropriate diagnostic workup can be completed, thus leading to an underestimate of case-fatality rates.

Signs and symptoms of influenza can vary from trivial to explosive. Although the disease is usually self-limiting, it can result in both severe incapacity and, when not properly treated, potentially fatal secondary pneumonia. Clearly, patients with comorbid conditions, the very young, pregnant women, and the elderly are at greater risk of suffering from complications from influenza. Those criteria, along with the adequacy of supply, form the basis for choosing who should be considered for vaccination each year. Because the symptoms of influenza can be quite similar to those of bacterial pneumonia, influenza may often be misdiagnosed as pneumonia. Generally, influenza is more self-limiting than pneumonia, although the infectivity and transmission of influenza from person to person can be substantial. The current threat of H5N1 influenza has resulted in increased human and avian surveillance and preparations for a possible pandemic (box 35.1).

Box 35.1

H5N1 Influenza. Clearly, of even greater concern is the potential for a new influenza A pandemic, as occurred in 1918 and more recently in 1958 and 1968, from a newly altered strain of avian influenza. With each additional bird-to-human case, modest genetic (more...)

The recent 2003 outbreak of severe acute respiratory syndrome (SARS; see chapter 53) emphasizes the importance of accurate and open surveillance and a coordinated response in controlling the spread of newly active influenza strains. The potential for global spread and the occurrence of worldwide epidemics of influenza (presumed to be transmitted to humans from domesticated or wild animals and then through close proximity to humans with symptomatic disease—generally to caregivers) points out the importance of continued surveillance for such episodes (Low and McGeer 2004). The lessons learned from the SARS epidemic reinforce the importance of proven traditional public health measures, such as finding and isolating cases, quarantining close contacts, and improving infection control practices (Bell 2004). Those methods, along with several other, less traditional efforts, were presumed to be part of the reason the epidemic was contained as promptly as it was (see table 35.1). However, because of the high case-fatality rate, the disease caused significant disruption throughout the world.

Table 35.1

Public Health Measures in the SARS Episode, 2003.

Chronic Respiratory Diseases: Nature, Causes, and Burden

COPD and asthma have very different diagnoses and causes; hence, they are discussed in separate sections. However, the treatments for these different chronic respiratory diseases share similarities, and that discussion is therefore combined. One of the difficulties in defining COPD on a worldwide basis is that three distinct levels are used, depending on the sophistication of the health care system in the country where the patient is being evaluated:

• Chronic bronchitis with and without obstruction, which may be part of the COPD diagnosis, is defined by the presence of chronic cough and phlegm for three months per year for two or more years and is generally assessed by standardized questionnaires.
• Obstructive airways disease is often assessed by reduced pulmonary function as measured by simple spirometry and the presence of a reduced ratio of the forced expiratory volume in one second (FEV₁) divided by the vital capacity (VC).
• For emphysema, which is also part of the syndrome of COPD, pulmonary function (changes in lung volume and reduced diffusion capacity), x-ray evidence of bullae formation, hyperinflation of the chest, and (with the use of high-resolution CT scanning) the presence of characteristic changes in lung architecture all may contribute to the diagnosis.

What is apparent is that not all these diagnostic procedures are applied equally, particularly in the developing world; thus, COPD may be seriously underreported. The 1998 Workshop Report by the WHO and the National Institutes of Health (NIH) on "Global Strategy for the Diagnosis, Management, and Prevention of COPD," developed as part of the Global Initiative for Chronic Obstructive Lung Disease (GOLD 2001), uses an international standard for defining the level of obstruction from COPD. This strategy should improve worldwide estimates. This standard definition will still require the use of equipment that measures pulmonary function (Buist 2002). Over the next several years, as the price and distribution of this equipment becomes more favorable and as more groups undertake the training in its use and in the interpretation of results from the tests, diagnostic uniformity will improve. Unfortunately, as pointed out by Aït-Khaled, Enarson, and Bousquet (2001), the applicability of these guidelines has not been effectively tested in developing countries.

In adults, COPD dominates all other chronic respiratory diseases in accounting for 2 percent to more than 10 percent of lost disability-adjusted life years (DALYs) on a worldwide basis. Its incidence increases dramatically with age (figures 35.1a and 35.1b). Of note, mortality from COPD is low before age 45. Over age 45, death rates increase from 50 to 200 per 10,000 individuals and are consistent across age groups in men and women, with the exception of death rates in women over age 80, which exceed those in men in that age group (figure 35.2).

Figure 35.1

Chronic Respiratory Diseases DALYs as a Percentage of World Totals

Figure 35.2

COPD by Age and Sex, Worldwide

Much of COPD in the developed world is related to cigarette smoking, and there is no question that progression of the disease is related to the number of cigarettes smoked and the years of smoking. Smoking cessation has been associated with reduced mortality from COPD, presumably through a mechanism that results in a modest improvement in pulmonary function that appears to be related primarily to the extent of chronic bronchitis and mucus hypersecretion (Scanlon and others 2000; Speizer and others 1989). Within a few years of stopping smoking, smokers' rate of decline of pulmonary function (that is, FEV₁) returns to the rate found in nonsmokers, although little of the lost pulmonary function is regained (Fletcher and others 1976). Similar effects are seen in the developing world. However, because smoking is far less prevalent in developing countries, especially among women, other exposures are related to the development of disease (see also chapter 46). One of the most important exposures, particularly for women, is to unvented coal-fired cooking stoves, starting during childhood and continuing into adult life (see chapter 42).

Because the interventions and treatments for COPD overlap with those for asthma, they will be treated together.

The diagnosis of asthma has been debated for centuries. Health care providers can generally agree on the diagnosis in the individual patient who is wheezing and in whom other etiologic factors are ruled out. They would also agree on the definition of the disease as an inflammatory response in the airways that results in variable and generally reversible airflow obstruction with or without treatment. However, depending on the training of health care providers, the nature of surveillance, the characteristics of a given community, and the particular environment of the community, the accuracy of the estimate of the prevalence of asthma in a community may vary much more. The reported prevalence of the disease may be based on no more than an answer to this question: "Has a provider ever told you that you (or your child) has had asthma?" The response to this question has been validated in a number of studies. In contrast, the diagnosis may depend on examination of the patient's chest, physiological testing, responsiveness to provocative stimuli to the airways, and specific response to therapy. Thus, estimates of community burden from asthma may depend on the threshold used in making the diagnosis.

Despite variations in diagnostic criteria, worldwide estimates of the asthma burden among adults have generally come from surveys within selected communities. In contrast to other adult respiratory diseases, the prevalence of asthma is relatively low (figures 35.1a and 35.1b). In adults, the DALYs for asthma are at a peak of about 2 percent of the total worldwide in people age 15 to 29, and they decline in each older age group. This pattern is also reflected in mortality rates, with the highest rates occurring in young people and equal rates in men and women about age 60. After age 60, reported rates of death caused by asthma in men begin to exceed those in women, and both become substantial. That shift reflects primarily either increasingly questionable diagnostic accuracy or misclassification of other obstructive respiratory diseases such as COPD.

Cost-Effectiveness of Interventions for COPD and Asthma in Developed Countries

Five recent overviews of the economics of chronic respiratory disease, COPD, and asthma (Friedmann and Hilleman 2001; Lee and Weiss 2002; Ruchlin and Dasbach 2001; Sullivan and Weiss 2001; Weiss and Sullivan 2001), in addition to many individual studies, focus on developed countries.¹ Only a limited number of studies use cost- or quality-adjusted life years (QALYs) saved as the outcome (others use life years saved). (Studies focusing on intermediate health outcomes and on cost minimization are not discussed here.) In general, costs in developing countries would be about 20 percent of those reported here, according to detailed unit cost data by region from WHO-CHOICE (Choosing Interventions That Are Cost-Effective) and on comparisons of respiratory drug prices from online pharmacies in the United States and from the International Drug Price Indicator Guide (http://erc.msh.org). The exceptions are interventions involving nondiscounted drugs that are still under strictly enforced patents, for which the costs in developing countries would be closer to those in the United States. Table 35.2 summarizes the results.

Table 35.2

Cost-Effectiveness of Interventions for Asthma and COPD in 2001.

Inhaled salbutamol (short-acting beta-2 agonist) is the first line of treatment for both intermittent asthma (daytime symptoms less than once per week, nocturnal symptoms less than twice per month, and normal spirometry between episodes) and COPD (mild to severe) in both developed and developing countries. This treatment became standard practice beginning in the 1970s, so there are no cost-effectiveness studies of salbutamol compared with placebo. This medical intervention is likely the most cost-effective one, but it is still likely to cost some thousands of dollars per life year saved in the United States.

The next line of treatment currently recommended for developing countries is inhaled corticosteroids (for example, beclomethasone) for mild to severe persistent asthma (disease ranging from daytime symptoms greater than once per week, nocturnal symptoms more than twice a month, and normal spirometry between episodes to daily frequent symptoms associated with severe obstruction) and inhaled ipratropium bromide for COPD. Both first-generation corticosteroids and ipratropium bromide are off patent. However, as pointed out by Chan-Yeung and others (2004), the use of corticosteroids either intermittently or chronically is commonly recommended in developed countries, where the background level of tuberculosis among patients is considerably lower. In developing countries with higher tuberculosis rates, corticosteroids must be used with greater caution.

Inhaled steroids cost about US$13,900 per QALY for mild to moderate asthma or when used in early treatment of COPD. The cost per QALY is likely to be lower for severe asthma, but ethical considerations render random controlled trials unfeasible.

No cost-effectiveness study could be found for ipratropium bromide compared with placebo. We estimate that the cost per QALY saved would be between one-half and two-thirds of that for a new-generation inhaled steroid such as fluticasone propionate. This estimate, which is based on the relative cost of the two drugs in the United States and assumes similar effectiveness of the two drugs, would put the cost of ipratropium bromide between US$6,700 and US$8,900 per QALY.

Most of the other interventions summarized in table 35.2 have a higher cost per QALY. For individuals who develop COPD related to a severe deficiency in alpha-1 antitrypsin, alpha-1 antitrypsin therapy is sometimes considered, at a cost of between US$45,000 and US$215,000 per life year.² The use of long-acting beta-2 agonists and leukotriene modifiers is now an accepted and integrated component of the treatment of moderate to severe asthma in the developed world. However, the cost savings for the developing world are difficult to demonstrate because the endpoints of studies using those drugs are often changes in spirometric testing, improved quality-of-life measures, steroid-sparing effects, or altered hospital admission rates.

Likewise, oral or intravenous steroids play a crucial role in the treatment of acute exacerbations in both asthma and COPD, but endpoint assessments in studies typically address decreases in the duration of hospital stays and increases in the use of emergency department facilities, which result in decreases in health costs in the developed world. Oral steroids are inexpensive, even by standards in developing countries, and in the short term might appear to be cost-effective, but they are associated with major medium- to long-term consequences and are not recommended as standard therapy.

Educational programs tend to be cost saving in developed countries, where uncontrolled exacerbations are extremely costly in terms of hospital care (six such programs are surveyed in Van Mölken and others 1992 and one in Ruchlin and Dasbach 2001). Similarly, exercise rehabilitation programs (six surveyed in Ruchlin and Dasbach 2001) can also be cost saving. WHO (2001) has commented on cost savings achieved by education programs for asthma from four different U.S. studies. Only one of these studies addressed cost per well year, which was estimated at US$71,500 in 2001 (Toevs, Kaplan, and Atkins 1984, cited in Ruchlin and Dasbach 2001). However, there are likely to be monetary savings from fewer workdays lost, which are not factored into this analysis.

WHO (2001) surveyed one self-management training program for chronic asthma in India (Ghosh and others 1998), which resulted in improvements in health status, reduced use of emergency departments and hospitals, and savings on health costs. Sudre and others (1999) pointed out that studies of education programs tend not to provide a good description of the actual program content and that a more systematic description of these interventions needs to be promoted to replicate best practice.

Long-term oxygen therapy is a life-prolonging intervention in advanced stages of COPD. Recent studies do not quantify the cost per QALY but instead compare different methods of oxygen delivery (cylinder or concentrator). These authors' crude estimate for long-term oxygen use is US$19,000 per life year saved.³ If the quality-of-life scores of patients on long-term oxygen were 0.8 or 0.6, the cost per QALY would be US$22,750 or US$31,700, respectively. (K. J. Smith and Pesce 1994, cited in the Harvard Catalogue of Preference Scores, assign a median score of 0.4 to quality of life for patients with severe COPD with high supportive care needs and poor functional status.)

In hospitals, mechanical ventilation in the intensive care unit has been estimated to cost US$35,000 to US$60,700 per QALY in 2001 (Anon and others 1999, cited in Ruchlin and Dasbach 2001). Studies suggest that noninvasive positive pressure ventilation, where it is feasible, is less costly than invasive mechanical ventilation for specific indications. Finally, costs of lung transplants are at a level scarcely affordable even in developed countries; Al and others (1998, cited in Ruchlin and Dasbach 2001) estimated costs at US$464,000 per QALY, and Ramsey and others (1995, cited in Ruchlin and Dasbach 2001) estimated costs at US$238,000 per QALY (in 2000 U.S. dollars).

All those interventions compare unfavorably with the cost-effectiveness of smoking prevention for preventing COPD (discussed in chapter 46). Smoking prevention is one of the most cost-effective health interventions that exists, and there is a strong case for moving resources from expensive curative interventions to that intervention. Likewise, prevention of COPD by switching the cooking source from unventilated stoves that burn biomass to either improved stoves or kerosene stoves is more cost-effective than treatment (see chapter 42).

Occupational Lung Disease and Other Respiratory Diseases

Although occupational lung diseases are often considered diseases of the industrial world, they are occurring with increased frequency in the developing world, where guidelines for worker safety are generally more lax or nonexistent. In addition, because of increased migration from rural areas to more urbanized centers and the transfer of major manufacturing activities from the developed market economy countries to the less developed countries, the number of employees with potentially harmful occupational exposures has increased exponentially in the past 30 years. The general discussion of occupation-related diseases is reviewed in chapter 60. We focus here on specific occupation-related lung diseases.

Occupational lung diseases are, for the most part, characterized as related to particular occupational exposures and generally fall into two broad pathophysiological types. One type may result in pulmonary fibrosis, which is manifested by restricted lung volume and decreased diffusion capacity on pulmonary function testing and increased interstitial pulmonary markings on chest x-ray. Certain occupational lung diseases, such as silicosis, are complicated by a substantially increased risk of tuberculosis, which contributes to the overall burden of respiratory disease in the developing world. The second pattern of occupational lung disease is that of obstructive airways disease, which may be reversible (occupational asthma) or irreversible (chronic bronchitis with or without obstruction or emphysema or COPD), in which the chest x-ray often is negative and the diagnosis is dependent largely on reported histories of exposures, symptoms, and pulmonary function testing.

There are few reliable estimates of the global burden of occupation-related respiratory diseases. Because of the lack of systematic surveillance in most developing countries, the few published estimates of occupation-related respiratory diseases have relied on selected studies involving particular industries that investigators have had unique opportunities to explore. For example, Trapido and others (1996) conducted a survey in a relatively small group of former mineworkers and found that approximately 55 percent had pneumoconiosis with or without tuberculosis. They estimated that about 25 percent of migrant and former mineworkers in South African gold mines with 15 to 25 years of exposure had occupational lung diseases. Loewenson (1999) pointed out the difficulties in making assessments of occupational risk throughout the African countries and suggested a series of methodological issues that need to be considered.

Leigh and others (1999) estimated the global burden of diseases related to occupational factors at 4.2 million to 10.0 million cases per year. If one subtracts the rates for established market economy countries, the total burden for the rest of the world is approximately 3.4 million to 9.1 million cases per year. Using limited data and applying rates from individual nations and regional groups of countries, the authors made an indirect calculation for the expected number of cases of occupation-related diseases globally. Figure 35.3 summarizes their estimates for pneumoconiosis and other chronic respiratory diseases by age and gender. Notably, these two categories of disease account for approximately 30 percent of all occupational diseases. The prevalence of these diseases increases with age and is higher among men.

Figure 35.3

Estimated Combined Pneumoconiosis and Other Occupation-related Chronic Respiratory Diseases

Asbestosis and asbestos-related cancers present a particular problem in developing countries. Asbestosis can manifest both as other interstitial lung disease, as described above, and as obstructive airways disease. In addition, occupational exposure is associated with the occurrence of lung cancer, and according to studies in developed countries, the rate of occurrence is synergistically associated with smoking. Because the cost of health care compensation in the developed world exceeds the potential profit from mining and manufacturing of asbestos products, much of the industry has moved to the developing world.

LaDou (2004) has recently summarized the status of the potential for reducing occupational exposure on a worldwide basis and suggests that upward of 10 million lives will be lost if the current lack of controls and continued increases in mining and manufacturing are not changed. In 2000, more than 2 million tons of asbestos products were produced, whereas 25 years earlier the total production was 350,000 tons each year. Except for the Russian Federation and Canada, virtually all the larger producers are in the developing world, where the recognition and reporting of health effects are less well established. The likelihood of reversing this trend and developing an international ban on asbestos use is small, particularly because it is the nations that produce more asbestos products that are, in fact, increasing consumption.

The economic burden of occupational lung diseases is surprisingly difficult to document. Most developed countries and some developing countries (for example, South Africa) have legislation protecting workers from exposure and compensating those who have contracted chronic conditions. In the United States, compensation payments from the Social Security Administration and the Department of Labor for black lung disease totaled US$1.6 billion in 1996 (NIOSH 1999). Data exist on compensation for claims for various occupational lung diseases for the United States and the European Union countries. However, claims data represent only a small fraction of the true economic cost (for example, not all workers make claims; compensation payments lag considerably). For the United States, the annual costs of complying with the revised respirator standards for 1993 were US$111 million for about 5 million workers needing to use a respirator (presumably these costs of prevention were far lower than the economic cost of unprotected work) (OSHA 1998). The primary treatment for affected workers is to remove them from the inciting exposures. (See chapter 60 for discussion of preventive strategies that need to be considered to reduce the risk of occupational disease.)

Some of the other major classes of adult respiratory diseases are discussed in other chapters: tuberculosis, in chapter 16; AIDS-related lung disease, in chapter 18; and lung cancer, in chapter 29. Other diseases that have been studied, particularly in the developed world, include the hypersensitivity or immunologically related pulmonary diseases most often associated with environmental exposures to specific inhaled antigens or interstitial inflammation and fibrosis, often of unknown origin. In the developing world, little systematic work has been done on these diseases to assess incidence or prevalence. These conditions probably occur considerably less frequently than asthma and COPD. However, they are likely to have a higher prevalence in developing countries than is reported in the developed world simply because of the presumed associations with exposures to organic dusts and the increased prevalence of malnutrition (see chapter 56), both of which are likely to occur in more rural and less developed areas of the world.

See chapters 16, 18, and 29 for interventions for tuberculosis, AIDS-related lung disease, and lung cancer, respectively. Managing immunologic and fibrotic respiratory diseases with medication is extremely difficult and expensive. Therapeutic trials often fail, presumably because the treatments are not aimed at a particular antigen. The most effective way of managing these respiratory diseases is to reduce exposure to the inciting agents, an approach that hinges on two strong premises, which are not always applicable in the developed world. First, the disease must be recognized as related to a common environmental contaminant encountered in an occupational or avocational exposure—for example, exposure to thermophilic actinomycetes in moldy hay or sugarcane results in farmer's lung, and exposure to bird feathers or droppings results in bird fancier's disease. Second, community resources must be directed toward educating the public about the importance of limiting exposure to these agents.

General Approach to Lowering Risk of Adult Respiratory Disease

Although interventions of various sorts are indicated for each of the disease categories discussed, these interventions are often costly and sometimes ineffective in lowering or preventing premature mortality. Thus, from an operational perspective, it is important to consider preventive and therapeutic strategies that will have greater societal effect than will the management of the manifestations of diseases as they arise in individuals. This approach applies to acute diseases (vaccination schemes to reduce the burden of influenza, in contrast to individual management of community-acquired pneumonia) and chronic diseases (smoking prevention and reduction programs, compared with availability of routine asthma medication). Primary prevention strategies should include efforts by multiple agencies of government and the community coming together to establish appropriate priorities for action. Four sources of exposure stand out: tobacco smoke, indoor smoke, outdoor air pollutants, and occupational exposure (see chapters 46, 42, 43, and 60, respectively). Of these, the most pressing and cost-effective is a cohesive policy to control tobacco smoking.

In conjunction with the International Union against Tuberculosis and Lung Disease (IUATLD) and selected universities and health institutions in various countries, WHO is developing the Practical Approach to Lung Health (PAL, previously known as the Adult Lung Health Initiative). The program is focused on improving primary care services, as well as appropriate referral to secondary health care facilities, for individuals with tuberculosis, acute respiratory infections (especially pneumonia), asthma, and COPD. Four countries (Chile, Morocco, Nepal, and South Africa) are serving as the pilot implementation sites (WHO 2003).

In Chile, where respiratory symptoms account for one-third of primary health care visits, a respiratory disease program was initiated in 2001 as part of ongoing efforts to strengthen primary health care. The pilot program was implemented in 15 centers. Standard formats are used to devise scores to determine follow-up for asthma and COPD. Sentinel centers are used to provide epidemiologic information. Influenza immunization coverage of the elderly and at-risk population has reached 85 percent (WHO 2003).

In Morocco, survey work done before establishing a PAL strategy showed that 31 percent of patients who consult primary health care centers present with respiratory symptoms. Of those patients, 85 percent have acute respiratory infections, 14 percent have chronic conditions, and 1 percent have tuberculosis. In Mexico, an IUATLD study implementing asthma control measures was shown to be cost-effective. Control of asthma improved, and the majority of patients experienced a decrease in the severity of asthma. The cost of asthma management decreased because of lower costs for emergency services and hospitalizations (WHO 2003).

Future Research Needs

One of the difficulties in quantifying the burden of respiratory diseases in adults is the inability to apply uniform methods of diagnosis across economies in which sophisticated diagnostic procedures are possible, let alone across less developed economies. The problems relate in part to differences in the language describing the same symptoms, levels of registration of census and disease reporting, availability of diagnostic procedures, and reluctance to make accurate estimates because of the cost of intervention strategies. Furthermore, unless controls on cigarette smoking are initiated, little progress in stemming the increasing burden of chronic respiratory diseases can be expected.

There are still a number of unanswered questions related to COPD, which remains the dominant respiratory disease in adults. The developing world provides some unique opportunities for research that go beyond the primary prevention that would result from better smoking control policies. Because not all smokers are at increased risk, the interaction of smoking with nutritional status (including micronutrient status), with genetic factors that determine susceptibility, and with respiratory infections may act as a precursor of susceptibility to environmental (ambient or occupational) pollution and personal (smoking) pollution. Similarly, the role of immunologic stimulation or immunocompetence needs further exploration as it relates to the development of asthma. Synergies between the conditions discussed in this chapter and other infections (particularly tuberculosis, but possibly others) may be especially important in the developing world. Finally, specific environmental conditions—such as altitude, heat and cold stress, and increased ambient pollution from rapid urbanization—and their effects on asthma and COPD should be explored.

Acute respiratory infections, specifically bacterial pneumonia, have not been addressed nearly as well for adults as they have been for children. For example, simple data on the prevalence of infecting organisms, typical susceptibilities, the ability to train ancillary workers in clinical diagnosis, and the correlation of clinical assessment with verified disease would be helpful in establishing the feasibility of assessment and treatment at home versus at a clinic or hospital, specifically in the developing world. Common etiologic agents in North America are common elsewhere; therefore, treatment of disease would be relatively inexpensive. Most community-acquired acute disease responds relatively well. Certainly, penicillin should be recommended as a first-line drug for community-acquired pneumonia. Educating local healers on the importance of initiating treatment earlier in the course of disease would translate into savings with respect to decreased days of work lost and reduced case-fatality rates. Follow-up monitoring and the development of hospital-based bacteriologic testing should be expanded to identify and control for the emergence of resistant bacterial strains.

Studies of asthma in the developed world have been extensive and of extremely high quality but are directed specifically toward the health care structures in which they are tested. Specific cost-effectiveness studies in the developing world should be done to see, for example, whether a focus on disease education and modification of risk factors in addition to medications outweighs simple administration of medications (with instructions on use). In the developed world, there is no question that an approach that is multitiered and involves multiple health care providers is the best, but we still do not have concrete evidence of where monies are best spent in the developing world. Another possible fruitful area of research is on education programs. Most of the literature relates to education programs for specific entities (for example, "asthma triggers") and their costs in developed countries. Education programs in developing countries that are multidimensional (smoking cessation, indoor air quality, vaccination) are likely to be relatively inexpensive and cost-effective. Better methods of educating local healers through the use of demonstration projects should be tested, as should more efficient distribution systems to make relatively inexpensive medication available. General increased awareness of the impact of symptoms on adults and of the potential for earlier intervention in a disease should also be explored and tested for their effects on reducing respiratory disease burdens.

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Footnotes

1

The survey of the cost-effectiveness of interventions below is based on a review of the University of York database (http://www​.york.ac.uk/inst/crd), combined with a Medline search (focusing mainly on data after 1996).

2

According to Hay and Robin (1991), cited in Ruchlin and Dasbach (2001). Akins and O'Malley (2000) have a much lower estimate, which probably does not include all the costs of screening and the like.

3

This estimate was calculated as follows: the MRC (1981) trials suggest that over five years the mortality in a randomized trial for patients with severe hypoxemia is 667 per 100,000 for those not treated with long-term oxygen, compared with 548 per 100,000 for those treated with long-term oxygen (reviewed in Crockett and others 2001). The cost per month of home oxygen is taken as US$400 (based on U.S. Medicare reimbursements in the early 1990s).