Clinical characteristics of adult asthma associated with small airway dysfunction.

Suboptimal asthma control is common despite modern asthma therapy. The degree of peripheral airway involvement remains unclear and poor medication delivery to these regions might be a contributing reason for this failure in obtaining adequate symptom control. A cohort of 196 adults (median (range) age 44 (18-61) years, 109 females, 54 ex-smokers, six current smokers) with physician-diagnosed asthma were recruited from primary care. Subjects were characterized clinically by interviews, questionnaires, skin prick tests (SPT) and blood eosinophil counts. Lung function was assessed by spirometry, impulse oscillometry (IOS) and nitrogen multiple breath washout (N2 MBW). IOS assessed peripheral airway resistance (FDR, frequency dependence of resistance). N2 MBW assessed global ventilation inhomogeneity (LCI, lung clearance index), specific indices of peripheral airway function (Scond × VT and Sacin × VT; VT, tidal volume), and inter-regional inhomogeneity (specific ventilation ratio). Never-smoking healthy cohorts of 158 and 400 adult subjects provided local reference values for IOS and N2 MBW variables, respectively. Peripheral airway dysfunction was detected in 31% (FDR or specific ventilation ratio) to 47% (Scond x VT) of subjects. Risk factors for peripheral airway dysfunction were identified. Among subjects with low FEV1 and either positive smoking history and/or blood eosinophilia (>4.0%), 63% had abnormality across all peripheral airway outcomes, whilst only one subject was completely normal. Abnormal peripheral airway function was present in a large proportion of adult asthmatics at baseline. Reduced FEV1, a positive smoking history, and/or blood eosinophilia identified "a small airway asthma subtype" that might benefit from peripheral airway targeted therapy.

Slow and fast lung compartments in cystic fibrosis measured by nitrogen multiple-breath washout.

Imaging studies describe significant ventilation defects across a wide range of cystic fibrosis (CF) related lung disease severity. These are unfortunately poorly reflected by phase III slope analysis-derived Scond and Sacin from multiple-breath washout (MBW). Methodology extending previous two-lung compartment model-based analysis is presented describing size and function of fast- and slow-ventilating lung compartments from nitrogen (N2) MBW and correlation to obstructive lung disease severity. In 37 CF subjects (forced expiratory volume in 1 s [FEV1] mean [SD] 84.8 [19.9] % predicted; abnormal lung clearance index [LCI] in 36/37, range 7.28-18.9) and 74 matched healthy controls, volume and specific ventilation of both fast and slowly ventilated lung compartments were derived from N2-based MBW with commercial equipment. In healthy controls lung emptying was characterized by a large compartment constituting 75.6 (8.4)% of functional residual capacity (FRC) with a specific ventilation (regional alveolar tidal volume/regional lung volume) of 13.9 (3.7)% and a small compartment with high specific ventilation (48.4 [15.7]%). In CF the slowly ventilated lung compartment constituted 51.9(9.1)% of FRC, with low specific ventilation of 5.3 (2.4)%. Specific ventilation of the slowly ventilated lung compartment showed stronger correlation with LCI (r2 = 0.70, P < 0.001) vs. Sacin (r2 = 0.44, P < 0.001) or Scond (no significant correlation). Overventilation of the fast lung compartment was no longer seen in severe CF lung disease. Magnitude and function of under- and overventilated lung volumes can be derived from routine N2 MBW in CF. Reported values agree with previous modelling-derived estimates of impaired ventilation and offer improved correlation to disease severity, compared with SnIII analysis.