Background Airway inflammation is considered to be important in asthma but is relatively inaccessible to study. Less Airway inflammation is a major factor in the pathogenesis of asthma. Mast cell and eosinophil infiltration, epithelial damage, and mucus production are characteristic features.' Direct examination of the inflammatory response should help to improve understanding of the pathogenesis and treatment of asthma.In patients with stable asthma bronchial biopsy and bronchoalveolar lavage have been used to study airway inflammation2' but discomfort, inconvenience, and risks limit their use. Examination of sputum is a less invasive alternative,5 but sputum cannot always be produced spontaneously. When sputum is not otherwise available induced samples may allow secretions from the lower airways to be sampled.Sputum induction by inhalation of hypertonic saline has been successfully used to diagnose Pneumocystis carinii pulmonary infections in patients infected with HIV.'We adapted this method for use in asthmatic subjects and examined (a) the success rate and safety of the method, (b) the reproducibility of cell counts, and (c) the differences in cell counts between normal and asthmatic subjects. Methods SUBJECTSSeventeen normal subjects and 17 subjects with asthma were selected from among the staff (adults) and asthmatic patients and their siblings (adults or children) at the clinics of the Firestone Regional Chest and Allergy Unit and the Health Sciences Centre. All were nonsmokers or ex-smokers of more than five years. None had spontaneous sputum or symptoms of a respiratory tract infection, or had been exposed to a seasonal allergen within the last month. The normal subjects had no past or current symptoms of asthma, a forced expiratory volume in one second (FEVI) >80% of predicted values,9 a ratio of FEV, to vital capacity >70%, and normal airway responsiveness to methacholine (provocative concentration of methacholine causing a 20% fall in FEV, (PC20) >8 mg/ml)'0 (table 1). The asthmatic subjects had a history of episodic dyspnoea with wheeze in the previous six months and a PC20 methacholine <8 mg/ml (15 patients) or a spontaneous variability in peak expiratory flow rate (PEF of >20% (two patients). All were taking an inhaled 2 agonist when needed; 15 were treated with inhaled corticosteroid (daily dose 200-3000 Mg) and one with prednisone 5 mg daily. Although asthma was stable in all subjects, control of the condition was good" in only five subjects; the remaining 12 had more asthmatic symptoms

Pulmonary function measures reflect respiratory health and predict mortality, and are used in the diagnosis of chronic obstructive pulmonary disease (COPD). We tested genome-wide association with the forced expiratory volume in 1 second (FEV1) and the ratio of FEV1 to forced vital capacity (FVC) in 48,201 individuals of European ancestry, with follow-up of top associations in up to an additional 46,411 individuals. We identified new regions showing association (combined P<5×10−8) with pulmonary function, in or near MFAP2, TGFB2, HDAC4, RARB, MECOM (EVI1), SPATA9, ARMC2, NCR3, ZKSCAN3, CDC123, C10orf11, LRP1, CCDC38, MMP15, CFDP1, and KCNE2. Identification of these 16 new loci may provide insight into the molecular mechanisms regulating pulmonary function and into molecular targets for future therapy to alleviate reduced lung function.

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This study shows that the increased risk of asthma conferred by 17q21 genetic variants is restricted to early-onset asthma and that the risk is further increased by early-life exposure to environmental tobacco smoke. These findings provide a greater understanding of the functional role of the 17q21 variants in the pathophysiology of asthma.