Introduction to asthma and phenotyping.

Asthma is an inflammatory disorder characterized by airway obstruction, airway hyperresponsiveness, and airway inflammation, all of which are variable among patients and variable in time within any specific patient. Understanding the mechanism that underlies this observed variability, and using that understanding to advance the science of asthma and the care of asthmatic patients, is an essential purpose of developing phenotypes. Clinical phenotypes have been used for decades, but overlap each other, and do not map cleanly to either pathophysiologic mechanism or with therapeutic response. Molecular phenotyping, although as yet only partially developed, offers the promise of dissecting the mechanistic underpinnings of the variability of asthma and of providing predictive therapeutics for the benefit of patients with this common and troubling disease.

Airway dysfunction in elite athletes--an occupational lung disease?

Airway dysfunction is prevalent in elite endurance athletes and when left untreated may impact upon both health and performance. There is now concern that the intensity of hyperpnoea necessitated by exercise at an elite level may be detrimental for an athlete's respiratory health. This article addresses the evidence of causality in this context with the aim of specifically addressing whether airway dysfunction in elite athletes should be classified as an occupational lung disease. The approach used highlights a number of concerns and facilitates recommendations to ensure airway health is maintained and optimized in this population. We conclude that elite athletes should receive the same considerations for their airway health as others with potential and relevant occupational exposures.

Phenotyping airways disease: an A to E approach.

The airway diseases asthma and chronic obstructive pulmonary disease (COPD) are heterogeneous conditions with overlapping pathophysiological and clinical features. It has previously been proposed that this heterogeneity may be characterized in terms of five relatively independent domains labelled from A to E, namely airway hyperresponsiveness (AHR), bronchitis, cough reflex hypersensitivity, damage to the airways and surrounding lung parenchyma, and extrapulmonary factors. Airway hyperresponsiveness occurs in both asthma and COPD, accounting for variable day to day symptoms, although the mechanisms most likely differ between the two conditions. Bronchitis, or airway inflammation, may be predominantly eosinophilic or neutrophilic, with different treatments required for each. Cough reflex hypersensitivity is thought to underlie the chronic dry cough out of proportion to other symptoms that can occur in association with airways disease. Structural changes associated with airway disease (damage) include bronchial wall thickening, airway smooth muscle hypertrophy, bronchiectasis and emphysema. Finally, a variety of extrapulmonary factors may impact upon airway disease, including rhinosinusitis, gastroesophageal reflux disease, obesity and dysfunctional breathing. This article discusses the A to E concept in detail and describes how this framework may be used to assess and treat patients with airway diseases in the clinic.

[The RHINASTHMA-Quality of Life Scale German Adapted Version: validation of a new disease specific quality of life scale for patients suffering from allergic rhinitis and bronchial hyperreactivity]. / Die RHINASTHMA-Lebensqualitätsskala German Adapted Version: Validierung einer neuartigen krankheitsspezifischen Lebensqualitätsskala für Patienten mit allergischer Rhinitis und bronchialer Hyperreaktivität.

BACKGROUND: In 2003 Baiardini et al. presented the RHINASTHMA questionnaire, which measures the impairment of quality of life in patients with rhinitis and asthma and takes the "united airway disease" model into its account. The aim of our study was to create a valid version of this questionnaire adapted for use with German-speaking subjects. METHODS: Datasets recorded for 85 patients were analysed for sensitivity, reliability and validity of the new questionnaire. For this purpose, as well as the symptom scores, disease-specific and generic quality of life questionnaires were also used as a measure of validity. RESULTS: A correlation analysis and Cronbach's alpha indicated that the RHINASTHMA scale is satisfactory from the aspect of reliability. Good validity was also shown in terms of discrimination and agreement for all items and scores. In addition, all the observed parameters reacted sensitively to clinical improvements of the health status. CONCLUSION: The RHINASTHMA questionnaire makes it possible to determine how badly the quality of life is impaired by rhinitis and asthma, based on the paradigm of "united airway disease".

Sideline management of asthma.

The timely, efficient, and effective sideline management of asthma must be based on an understanding of the disease processes, awareness of evidence-based therapeutic intervention, and thorough knowledge of the individual athlete's past and present medical history. There is accumulating evidence that exercise-induced airway narrowing, if unrecognized or inadequately treated, can progress to a severe life-threatening status and should always be viewed as a potential medical emergency. A widening range of therapeutic measures is currently available to prevent and treat exercise asthma, and treatment must be tailored to the individual circumstances in order to optimize response.

Bronchial hyperresponsiveness in patients with sarcoidosis.

OBJECTIVE: To study bronchial hyperresponsiveness (BHR) in patients with sarcoidosis. METHODS: Twenty freshly diagnosed patients with sarcoidosis were evaluated. Progressively increasing concentrations of methacholine were administered using a standard five-breath dosimeter protocol, and spirometry performed after each challenge. BHR was expressed as PC20 (provocating concentration of methacholine resulting in 20% fall in forced expiratory volume in first second). All patients were nonsmokers, had no other concurrent cardiopulmonary disease, and were not on any specific treatment for sarcoidosis. RESULTS: Borderline (PC20 4.0-16.0 mg/mL), mild (PC20 1.0-4.0 mg/mL) and moderate to severe (PC20 <1.0 mg/mL) BHR was documented in three (15%), one (5%) and five (25%) patients respectively. Patients with BHR were similar to those having normal reactivity in terms of age, gender, disease duration and results of pulmonary function testing. All patients with endobronchial disease had BHR. CONCLUSION: BHR may be seen in several patients of sarcoidosis and could possibly contribute to decline in lung function.

Cough and bronchial responsiveness in firefighters at the World Trade Center site.

BACKGROUND: Workers from the Fire Department of New York City were exposed to a variety of inhaled materials during and after the collapse of the World Trade Center. We evaluated clinical features in a series of 332 firefighters in whom severe cough developed after exposure and the prevalence and severity of bronchial hyperreactivity in firefighters without severe cough classified according to the level of exposure. METHODS: "World Trade Center cough" was defined as a persistent cough that developed after exposure to the site and was accompanied by respiratory symptoms severe enough to require medical leave for at least four weeks. Evaluation of exposed firefighters included completion of a standard questionnaire, spirometry, airway-responsiveness testing, and chest imaging. RESULTS: In the first six months after September 11, 2001, World Trade Center cough occurred in 128 of 1636 firefighters with a high level of exposure (8 percent), 187 of 6958 with a moderate level of exposure (3 percent), and 17 of 1320 with a low level of exposure (1 percent). In addition, 95 percent had symptoms of dyspnea, 87 percent had gastroesophageal reflux disease, and 54 percent had nasal congestion. Of those tested before treatment of World Trade Center cough, 63 percent of firefighters (149 of 237) had a response to a bronchodilator and 24 percent (9 of 37) had bronchial hyperreactivity. Chest radiographs were unchanged from precollapse findings in 319 of the 332 with World Trade Center cough. Among the cohort without severe cough, bronchial hyperreactivity was present in 77 firefighters with a high level of exposure (23 percent) and 26 with a moderate level of exposure (8 percent). CONCLUSIONS: Intense, short-term exposure to materials generated during the collapse of the World Trade Center was associated with bronchial responsiveness and the development of cough. Clinical and physiological severity was related to the intensity of exposure.

Perception of airway narrowing in a general population sample.

In epidemiological studies, defining asthma as the presence of airway hyperresponsiveness (AHR) plus recent symptoms leaves two groups of subjects whose clinical significance is unclear: those with asymptomatic AHR, and those with symptoms only. The aim of the study was to determine whether subjects with symptoms only differ from the normal and asthmatic groups in the perception of airway obstruction. Six hundred and ninety seven adults completed a questionnaire of symptoms and underwent bronchial challenge with histamine to induce airway obstruction. Recent symptoms included wheeze and morning chest tightness in the last 12 months. AHR was defined as a provoking dose of histamine causing > or = 20% fall in forced expiratory volume in one second (PD20FEV1) <3.9 micromol. At the end of the challenge test, subjects who felt wheezy or tight in the chest marked a value from 0 to 10 on a modified Borg scale, to describe the severity of the sensation. Subjects with asymptomatic AHR did not differ significantly from subjects with AHR plus recent symptoms (current asthma) either in the mean fall in FEV1 or in the median Borg score. In subjects with symptoms only, the mean Borg score was not significantly different from that of the asthmatic subjects, although mean fall in FEV1 differed significantly (p<0.0001). In subjects with symptoms only, chest tightness correlated significantly with the fall in forced vital capacity (FVC) (p= 0.011), but not with the fall in FEV1. Subjects with asymptomatic airways hyperresponsiveness were not poor perceivers of airway narrowing, but may underreport their symptoms. Subjects with symptoms only may have enhanced perception of small changes in lung function, particularly in forced vital capacity.

Comparison of three definitions of asthma: a longitudinal perspective.

In epidemiological studies, defining "current asthma" as the presence of both wheeze in the last year and airway hyperresponsiveness (AHR) identifies children with more severe abnormality compared with children with either measure alone. The predictive value of this definition of asthma and other commonly used definitions have not been compared. In 1982, we enrolled a random sample of 718 schoolchildren aged 8-10 years, and in 1992, we restudied a representative sample of 407. On both occasions, we measured wheeze, medication use, morbidity, AHR, and atopy. We compared three asthma definitions-"current asthma," recent wheeze, and doctor-diagnosed asthma. Approximately 70% of subjects classified by each definition remained consistently classified in 1992. However, the current asthma definition distinguished a group with more severe illness after 10 years than did the other asthma definitions. The current asthma definition not only differentiates children with more severe asthma, but also differentiates those with a more severe prognosis.

Reactive airways dysfunction syndrome.

Two types of occupational asthma have been identified and are distinguished by whether they appear after a latency period. Asthma without a latency period is best illustrated by irritant-induced asthma. The reactive airways dysfunction syndrome is a subset of irritant-induced asthma. Although case reports appeared in the literature before 1985, the term reactive airways dysfunction syndrome was coined in 1985. Since that report a number of case reports of asthma-like illnesses developing as the direct consequence of massive toxic inhalation exposure have been published. Not all experts, however, are certain that reactive airways dysfunction syndrome is a real and distinct clinical entity. Most studies and reviews, although acknowledging the current gap in our knowledge of the epidemiology, pathogenesis, and pathologic findings, conclude that the available scientific evidence supports the conclusion that reactive airways dysfunction syndrome and irritant-induced asthma are valid disorders.