Natural History Of Asthma Research Articles

Problems and possibilities in understanding the natural history of asthma

Problems and possibilities in understanding the natural history of asthma

The role of viral infections in the natural history of asthma

Viral infections have been related to the inception of recurrent wheezing illnesses and asthma in infants and are probably the most frequent cause of exacerbations of established disease in older children and adults. The well-recognized clinical effects of viral infections are mainly caused by virus-induced immune responses. Clinical studies of natural and experimentally induced viral infections have led to the identification of mechanisms of inflammation that could be involved in producing airway obstruction and lower airway symptoms. In addition, host factors that are associated with more vigorous viral replication or severe clinical illness are beginning to be identified. Advances in molecular virology and our understanding of immune responses to viral infections may lead to the development of new strategies for the prevention and treatment of virus-induced respiratory disorders. (J Allergy Clin Immunol 2000;106:201-12.)

Unmet needs in the treatment of asthmatic children and adolescents: 1.

The paediatric asthma guidelines have been successful in providing a uniform approach to the management of asthma for the medical profession as a whole. Unfortunately, the guidelines were generated without input from patients themselves and consequently do not consider issues that are important to patients such as a preference for oral treatment. Asthma is a heterogeneous group of conditions and the guidelines do not sufficiently define subgroups of patients and their particular needs. As a result, there has been a tendency to assume that all wheezing in infancy is asthma and this had led to gross overtreatment in certain patients. In contrast, severe asthma often remains underdiagnosed and undertreated. The most recent revision of the guidelines has classified asthma in terms of the patterns of disease; infrequent episodic, frequent episodic and chronic persistent. The treatment required for each of these groups is clearly defined and there is no need for stepwise therapy. Other changes to the guidelines will occur and are needed. None of the treatments available can modify the natural history of asthma; they control the symptoms not the disease process. Evidence from bronchial biopsies suggests that both inflammation and remodelling occur early, even before the first symptoms appear. We need to look for the factors in early life that predict which children will go on to develop asthma and intervene at that stage. Anti-histamines and leukotriene receptor antagonists may be interesting as interventions in that respect. Two important unresolved issues are to understand what drives remodelling and inflammation, and to look at early life origins of asthma. These approaches may provide effective therapeutic targets and, ultimately, a means of prevention.

Natural history of asthma: a 23-year followup of college students

A 23-year followup study of 1,601 college students who were initially evaluated for evidence of asthma and allergic rhinitis by direct interviews, physical examination, laboratory tests, and repeated questionnaires was conducted. The individuals were located through addresses from the alumnae office. Of these, 1,021 (64%) returned their completed questionnaires and these included 738 (72%) who had allergy skin tests as freshmen. A similar proportion of our total population of 1,021 were skin tested as freshmen compared with the original study population of 1,836 in the freshmen year (72% versus 68%). This difference was not statistically significant. Among these 738 alumnae, with a mean age of 40 years, there were a total of 84 with a history of asthma. At the time of the 23-year followup, 44 (52%) were considered to have active asthma and 40 (48%) were symptom free. A majority (85%) of those with inactive asthma were symptom free for 5 years or longer. Of those with active asthma, 50% felt they were improved, 39% unchanged, 9% felt worse, and 2% were unknown. Atopy was a non-prognostic indicator of asthma outcome as determined by scratch skin testing as college freshmen. New asthma occurred in 36 (5.2%) of those at risk to develop new asthma in this 23-year period for a rate of 0.23% per year. This 23-year followup study demonstrates that the cumulative prevalence of asthma continues to increase as the individuals become older. The asthma symptoms were no longer present or were improved in about three-fourths of the asthma subjects in this 40-year-old age group. Of the remainder, most symptoms were unchanged and a small number felt worse.

How the Discrepancy between Symptoms and Peak Expiratory Flow Rate Influences Evaluation of Asthma Severity

Recent asthma guidelines recommend the assessment of severity levels based on the most severe symptoms and peak expiratory flow rate (PEFR). Discrepancies are frequently encountered in the use of these variables in determining the severity levels of asthmatics. The objective of this study was to determine the difference in asthma severity levels as assessed by either symptoms alone or by PEFR alone, as compared with the assessment by the asthma guidelines. Severity levels that were determined by recent asthma guidelines for 60 asthmatic patients were reassessed, based on symptoms alone and PEFR alone. They were compared for any significant differences to the asthma guidelines. Asthmatics were aged between 15 and 70 (mean 34) years, and 63.8% were females. Severity levels by symptoms alone were different from the guidelines in 27 cases (45%). Of these, 89% showed a tendency toward higher severity levels. Severity levels by PEFR alone were different in only three cases (5%). In both comparisons, differences of severity levels were significant (P<0.0001), but assessment by symptoms alone showed more deviation (x(2) =162.1) than PEFR alone (x(2) =73.1). The study documented significant discrepancies in asthma severity assessed by symptoms alone and PEFR alone, when compared to the recent asthma guidelines. Severity assessed by symptoms alone showed lower levels, and the use of PEFR tended to categorize some asthmatics into a more severe level.

The natural history of asthma in adults: The problem of irreversibility

Asthma is common, affecting 5% to 10% of adults; asthma is progressive, leading to irreversible obstruction in 80% of elderly patients; and asthma is complex, often complicated by coexisting lung diseases. This loss of lung function results from 4 independent pathologic conditions: (1) airway remodeling, especially in the small airways, from the lymphocytic-eosinophilic inflammation that characterizes asthma; (2) bronchiectasis; (3) postinfectious pulmonary fibrosis; and (4) emphysema and chronic bronchitis from tobacco smoke. Deterioration in lung function develops faster in nonallergic patients with intrinsic asthma during the period shortly after onset of asthma and in older patients. About 4% of patients die of asthma, and most are elderly. Death most often results from complications of irreversible obstruction or cardiotoxicity of bronchodilator therapy. More research is needed to improve therapy for preventing remodeling of small airways, to confirm the frequency of bronchiectasis and postinfectious fibrosis and to determine their causes, and to develop diagnostic criteria to identify these complications. Meanwhile, clinicians treating adult asthmatic patients need to be aggressive in preventing the damage from cigarette smoke; in immunizing for influenza and pneumococcus infection and identifying and treating respiratory infections, particularly at times of acute exacerbations; in diagnosing and managing bronchiectasis; and in objectively confirming the efficacy of asthma therapy to prevent illness from overtreatment with glucocorticoids and bronchodilators. (J Allergy Clin Immunol 1999;103:539-47.)

Alternative agents for anti-inflammatory treatment of asthma

Recent guidelines for the management of asthma have emphasized the role of inflammation in persistent asthma. Medications with anti-inflammatory properties are recommended as the primary long-term-control medications. Of the available choices of long-term-control medications, inhaled corticosteroids are the preferred medication. A literature review of the available studies supports this recommendation of inhaled corticosteroids as the preferred agents for long-term control. Other long-term-control medications—specifically nedocromil, theophylline, and leukotriene modifiers, but not cromolyn—can supplement the beneficial effect of inhaled corticosteroids on pulmonary function and symptom control. Long-acting β 2-adrenergic agonists can also provide an additive clinical benefit to inhaled corticosteroids on symptom control and pulmonary function, but they do not provide additional anti-inflammatory effect. Extended long-term studies of each of the long-term-control medications with anti-inflammatory actions are needed to assess their specific effect on airway remodeling and on the natural history of asthma. (J Allergy Clin Immunol 1998;102:523-S35.)

Bronchial hyperresponsiveness, atopy, airway inflammation, and asthma.

Airway inflammation particularly with eosinophil infiltration is an almost invariant feature of asthma, though it may not be exclusive to asthma. BHR and atopy are common phenomena in asthmatics but not invariably so. Allergen-induced late asthmatic responses can increase non-specific hyperresponsiveness and bronchial responsiveness in turn is, at least from some studies, correlated with the degree of airway inflammation. Atopy is a major risk factor for the development of asthma and its persistence from childhood into adulthood. Airway inflammation occurs very early in the natural history of asthma. No therapeutic intervention in established asthma has been shown to achieve a cure or even modify the natural history of the disease. Therefore, further studies are urgently required to identify whether strategies of early intervention to prevent the development of airway inflammation will modify the natural history of the disease.

Longitudinal Measurement of Airway Hyperresponsiveness in Selected Subjects with Persisting Pulmonary Symptoms

The relationship between airway hyperresponsiveness and pulmonary symptoms was examined longitudinally in 52 subjects. Subjects were part of a larger study, the Natural History of Asthma, and had repeated measures of airway hyperresponsiveness using methacholine. Atopy was determined using skin tests and serum IgE levels. The subjects completed a standardized respiratory questionnaire. Each subject reported respiratory and pulmonary symptoms at either their initial or follow-up visit. The subjects did not, however, have a physician-confirmed diagnosis of asthma. Subjects were divided into groups according to the current status of their respiratory symptoms. The four groups included subjects who were initially normal but developed respiratory symptoms at follow-up; subjects who had symptoms at all visits; subjects with respiratory symptoms at their initial visit but who had no symptoms at follow-up; and subjects who had respiratory symptoms prior to their initial visit and who did not have a recurrence during follow-up. There was no statistical difference in airway hyperresponsiveness, IgE, or skin test scores at the initial visits. Subjects who had airway responsiveness were significantly more atopic than subjects who did not have airway responsiveness. Subjects were classified as "consistently positive," "variable," or "consistently negative" responders according to the pattern of methacholine-induced airway hyperresponsiveness. Overall, among the four groups, 33% were consistently positive at all visits, 43% were variable, and 22% were consistently negative. Airway hyperresponsiveness was statistically associated with atopy, but not necessarily associated with questionnaire-based respiratory symptomatology. These factors need to be considered in epidemiological studies of asthma utilizing respiratory questionnaires.

Occupational asthma--a model to study the natural history and pathogenic mechanisms in asthma.

Occupational agents can give rise to asthma either through producing specific IgE antibodies or through some as yet unidentified immunological mechanism. Study of pathogenic mechanisms of occupational asthma can generate very useful information on the pathogenesis of nonoccupational asthma. Occupational asthma also provides an ideal model to study the natural history of asthma. As the agent responsible for asthma is known, it is possible to design a study to investigate predisposing host factors and level of exposure and their interaction in determining the onset, the severity, and the outcome of the disease.

Natural history of asthma in childhood--a birth cohort study.

A cohort of 67 babies at risk of developing atopic disorders was followed up prospectively for 11 years. Clinical assessment and skin prick allergen sensitivity testing were performed annually over the first five years. At 11 years the cohort was restudied, symptoms were assessed by questionnaire, and bronchial reactivity (BHR) to histamine was measured. On the basis of skin testing, 35 children were atopic and 32 remained non-atopic. The expression of atopy increased with age. The lifetime prevalence of eczema, wheeze, and hay fever were 46%, 63%, and 56% respectively. The yearly period prevalence of hay fever increased with age, that of eczema declined, while that for wheeze showed a bimodal distribution with a peak before the age of 2 years and a gradual increase thereafter. Of the 21 children who wheezed before their second birthday, most never wheezed again and did not show BHR at 11 years. Of the 21 children whose first wheezing was after 2 years of age, 17 were still wheezing at 11 years and 12 showed BHR. Of the children who wheezed before 2 years of age, 10 were or became atopic, compared with 20 of the 23 children who wheezed at 11 years. These findings suggest that childhood asthma is a heterogeneous condition with atopy being strongly associated with the persistence of wheeze.

Bronchial asthma at high altitude: a clinical and laboratory study in Addis Ababa.

In a study designed to throw light on the natural history of asthma in Ethiopia, 91 patients living at 2500 metres and attending asthma clinics in Addis Ababa underwent spirometric and skinprick testing. Only eight had had symptoms of asthma before the age of 16. Sixty two had a history of allergic rhinitis and 16 had a family history of allergic rhinitis; 33 had a family history of asthma. In 30 cases asthma was worse from August to October. All patients had tried traditional remedies, usually without success; and all took modern drugs, oral combination bronchodilators being the most frequently used.

Trends in Australian mortality of asthma, 1979-1985.

Trends in Australian mortality rates that have been ascribed to asthma and to non-tuberculous, non-malignant respiratory diseases were examined for the period 1979-1985. Mortality rates of asthma and respiratory diseases increased substantially from 1979 to 1985, and in the case of asthma, the crude death rate in 1985 was higher than at the peak of the "epidemic" of the 1960s. The increase in mortality of asthma was most pronounced in those of greater than 60 years of age (from 11.5 per 100,000 such population in 1979 to 22.9 per 100,000 such population in 1985). Asthma mortality rates in five- to 34-year-old persons increased, although there were marked yearly fluctuations, and deaths of asthma in this age-group comprised only a small percentage (13% in 1985) of all deaths of asthma. Reasons that are considered for the rising death rate of asthma include changes in diagnostic fashion; an increase in the incidence or a change in the natural history of asthma; and an increased case fatality rate. With the presently-available data, it is not possible to distinguish among these possible explanations.

The natural history of asthma

There are numerous problems in studying the “natural history” of a disorder such as asthma. One of the characteristic features of the disease is its responsiveness to therapy. When populations that have ready access to medical care are studied, the inllucnces of treatment on the long-term course of the discasc may be dif6cul: or even impossible to determine. The best accomplishment under these circumstances is a description of the course and prognosis of the disorder in semi: pretlefined population sample receiving “ordinary” medical attention. A second problem relates to the inherent variability of the disea.sc regardless of therapy. Although the traditional epidemiologic approaches used to examine the evolution of chronic disorders may be applicable to very persistent and refractory forms of asthma, such approaches are of qucstiona’3le usefulness in mild or very intermittent forms of the disease. In the latter cases: there l:s total dependence on the subjects’ recall of past evetts, unless the study has been designed specifically I:O examine patients at the time of acute symptomatic exacerbations. This is less of a problem when a series of clinical cases arc being examined than in general population samples. but it is doubtful that cases being followed in most research-oriented ciinics are representative of the total asthma problem. The most difficult problem in studying asthma is the lack of generally accepted diagnostic criteria for the disease, particularly criteria that are applicable to krge scaie epidemiologic investigations. Even in children, [here is no clear distinction between “chronic bronchitis” and “asthma.” A history of wheezing is oue of the most characteristic findings in children with Bronchitis,’ and childhood chronic bronchitis as well as asthma is related to allergy skin test reactivity.‘, 3 A!so, children frequently ha\Tc wheezing complaints ihat are not associated with any clinical diagnosis; these are also more common among atopic than non-

Future Prospects for Pharmacologic Studies of Asthma

This is an area full of promise. Ingram (oral communica­ tion, this conference) has elsewhere demonstrated the ways in which it should be investigated, but one should not forget that: 1. Hyperreactivity is not synonymous with asthma and is not systematically predictive of asthma. Hyperreactivity is one of several factors suggesting the presence of asthma and alone is not sufficient evidence for the condition. 2. Hyperreactivity is one piece of information among many others. Without information on hyperreactivity, the correlations between the other variables may be clear and always in the same direction. 3. Hyperreactivity is far from being the only component of the physiopathology of asthma, of the attack, or of bronchospasm. The mechanisms of edema, hypersecretion, and dissecretion have not been studied sufficiently, mainly because of the limitations of currently available technology. Advances in biomedical research are now enabling detailed investigation of the physiology and biochemistry of hyper­ reactivity. It should also now be subjected to epidemiologic research to understand its place in the natural history of asthma in general populations in relation to age, sex, eth­ nicity, way of life, pollution, occupation, etc.

Natural History of Asthma in Patients Requiring Long-term Systemic Corticosteroids

To study the natural history of corticosteroid-dependent asthma, we evaluated 40 randomly selected adult patients with severe asthma who were refractory to management with inhaled corticosteroids and bronchodilators and who required long-term prednisone therapy (mean duration, 6.2 +/- 5.1 years). During long-term observation, 13 patients (32.5%) significantly improved; ten (25%) of these tolerated discontinuation of long-term prednisone use and three (7.5%) had decreased prednisone requirements. Three patients (7.5%) had increased requirements for prednisone. Twenty-four patients (60%) had generally unchanged, long-term prednisone requirements; of note, eight of these had significant, but temporary intervals (mean, 3.2 years) when they could be managed without prednisone. Patients with mixed asthma were more likely to tolerate discontinuation of long-term prednisone; no other factors studied were predictive of the course of asthma. Although prior to our care many patients had a history of numerous emergency room visits and hospitalizations (some for life-threatening episodes of status asthmaticus), there were few emergency room visits and hospitalizations while under strict management by our service. Variations observed in the natural history of corticosteroid requirements in asthma must be considered in designing studies seeking to evaluate efficacy of new experimental therapies for asthma.

Natural history of asthma in patients requiring long-term systemic corticosteroids

Natural history of asthma in patients requiring long-term systemic corticosteroids

The natural history of asthma in childhood.

The incidence and prognosis of childhood asthma and wheezing illness (AW) was studied using data obtained at ages 7, 11, and 16 from a national cohort of 8806 children born in 1958. By the age of 16, 24.7% were reported to have experienced at least one episode of AW. In 18.3% AW had started before the age of 8, but only 4.2% continued to have symptoms in later childhood. A further 3.6% began to have AW between the ages of 8 and 11, and 2.8% began between the ages of 12 and 16. Of those with AW at age 7, 28.3% had symptoms at 11 and 16.5% at 16; these proportions were about doubled if AW at 7 had been severe. The associations between natural history and a large number of perinatal, social, environmental, and medical factors were examined. Those which predicted the onset of AW after the age of 7 were: male sex of child; mother aged 15-19 at child's birth; history of pneumonia, whooping cough, throat or ear infections or tonsillectomy; eczema, allergic rhinitis; and periodic vomiting or abdominal pain.

The Practical Management of Asthma.

Making the diagnosis; natural history of asthma; precipitating factors in asthma; management of chronic asthma; childhood asthma; asthma in general practice; role of inflammation; methods of drug delivery; physical and psychological treatments; patient education.

A new look at adult asthma

Understanding of the natural history of asthma is hampered by the lack of precise definitions. A new definition of severe acute asthma is proposed with primary emphasis on the circulatory disturbances. The natural history of severe acute asthma and the value of steroid therapy are re-examined in the light of the new definition.