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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 (N 2 MBW). IOS assessed peripheral airway resistance (FDR, frequency dependence of resistance). N 2 MBW assessed global ventilation inhomogeneity (LCI, lung clearance index), specific indices of peripheral airway function (S cond × V T and S acin × V T ; V T , 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 N 2 MBW variables, respectively. Peripheral airway dysfunction was detected in 31% (FDR or specific ventilation ratio) to 47% (S cond x V T ) of subjects. Risk factors for peripheral airway dysfunction were identified. Among subjects with low FEV 1 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 FEV 1 , a positive smoking history, and/or blood eosinophilia identified "a small airway asthma subtype" that might benefit from peripheral airway targeted therapy.

Introduction: Cystic fibrosis (CF) lung disease is characterized by uneven ventilation distribution, which can be measured by the N 2 multiple breath washout (MBW) and the vital capacity single breath washout (VC SBW) test. A MBW test is more time consuming than a VC SBW test. Aims: To determine the prevalence of abnormal MBW and SBW test results in teenagers and adults with CF. Methods: Spirometry and triplicates of N 2 MBW and N 2 VC SBW were performed in 31 subjects (9 females) with CF, aged 13-45 yrs (median 23 yrs) using the Exhalyzer D washout device. Washout results were related to 400 healthy control subjects for N 2 MBW and 224 for N 2 VC SBW. Results: FEV 1 was abnormal in 7/31 (23%) subjects, VC SBW phase III slope (S III ) was abnormal in 20/31 (65%), LCI 29/31 (94%), S cond 30/31 (97%), S acin 24/31 (77%) and fast-to-slow regions specific ventilation ratio in 30/31 (97%). Among the 11 subjects with normal VC SBW S III , 10 (91%) showed abnormal MBW results. Consclusions: Abnormal N 2 VC SBW S III was seen in the majority of teenagers and adult CF subjects with normal FEV 1 , suggesting additional value of this method, but normal S III does not exclude pathological MBW outcomes.

Introduction: We have recently demonstrated a high frequency (almost 50%) of abnormal small airway function assessed by nitrogen (N 2 ) multiple breath washout (MBW) test in an adult asthma population of 196 subjects. The N 2 vital capacity single breath washout (VC SBW) test is far less time consuming than N 2 MBW and could be an option in a busy asthma clinic if showing a good concordance with N 2 MBW results. Aims: To compare the prevalence of abnormal ventilation distribution assessed by the N 2 VC SBW and the N 2 MBW test in adult asthma. Methods: 194 (107 females) adult asthmatics aged 18-61 years performed spirometry and N 2 MBW plus VC SBW using the ExhalyzerD washout device. Normative values for N 2 MBW and VC SBW were calculated from 400 and 224 healthy controls, respectively. Results: Abnormal N 2 S III was found in 48/194 (24.7%) subjects. LCI was abnormal in 86/194 (44.3%) subjects, S cond in 91/194 (46.9%) subjects, and S acin in 81/194 (41.8%) subjects. Less than half of the subjects with abnormal LCI showed also abnormal N 2 S III (38/86; 44.2 %) vs. 10/108 (9.3 %) among those with normal LCI (p Conclusions: This study shows a markedly higher sensitivity of the N 2 MBW vs. N 2 VC SBW test in detecting peripheral airway involvement in adult asthma, indicating limited utility of the N 2 VC SBW test in asthma monitoring.

Nitrogen multiple breath washout (N2 MBW) is a sensitive method to identify peripheral airway involvement in asthma, but is a time-consuming test. The N2 vital capacity single breath (VC SBW) test offers greater time efficiency, but concordance with N2 MBW is poorly understood. The prevalence of peripheral airway abnormality was determined by N2 MBW and N2 SBW tests in 194 asthmatic subjects aged 18-1 years. N2 MBW data were related to findings in 400 healthy controls, aged 17-71 years, while N2 SBW data were compared to findings in 224 healthy controls, aged 15-65 years, to derive equipment-specific reference values. Amongst asthmatic subjects, relationships between N2 SBW and N2 MBW outcomes were studied. N2 SBW relationship with clinical history, spirometry, blood eosinophils and fraction exhaled nitric oxide (FENO) data was also explored. The prevalence of peripheral airway involvement (i.e. abnormal ventilation distribution) determined by N2 SBW-derived phase III slope (N2 SIII ) was 24·7%, compared to 44% determined by N2 MBW-derived lung clearance index (LCI) (P

Particles in exhaled air (PEx) generated from the respiratory tract lining fluid can be counted and sampled by the PExA method. Previous study findings with PExA indicates that number of PEx decreases with increasing airway disease severity, defined by Spirometry. We aimed to determine if decreased number of PEx correlates with indices associated with peripheral airway dysfunction in adult asthma. 173 adults (99 females), median age 44 (range 18-61) years, with physician-diagnosed asthma participated. Peripheral airway dysfunction was assessed from FEV 1 /FVC, frequency dependence of resistance (R5-R20) using impulse oscillometry (IOS) and global ventilation inhomogeneity (Lung Clearence Index;LCI) likewise specific peripheral airway ventilation inhomogeneity (Sacin and Scond) using nitrogen multiple breath washout (N 2 MBW). Subjects exhaled into the PExA instrument using a breathing maneuver allowing for airway closure and re-opening. Number of PEx was counted by an opticle particle counter in the PExA instrument. Reference values were obtained from 158 (IOS) and 400 healthy controls (N 2 MBW), respectively. Upper/lower limit of normal was defined as +/- 1.96 SD. PEx mass (pg/L) was compared with the lung-function measurements, using the Mann-Whitney test. PEx was decreased in asthmatics with abnormal vs. normal LCI (median 753 vs. 1315 pg/L, p=0.011) and with abnormal vs. normal Sacin (median 615 vs. 1350 pg/L, p Abnormal ventilation in or near the acinar zone in the peripheral airways is closely related to low numbers of exhaled particles from the respiratory tract, suggesting a very distal origin of the particles.

Background: Lung clearance index (LCI) from N 2 multiple breath washouts (MBW) is known as a sensitive marker of peripheral airway obstruction (ERJ 2013;4:507). Airway function declines with age but the association between ageing and peripheral airway function is not fully known. Aim: To see if airway function decline with ageing is more closely related to the LCI than to the FEV 1 /FVC ratio from spirometry or the residual volume/total lung capacity (RV/TLC) ratio obtained by body plethysmography. Subjects and methods: 313 (160 males) subjects without any history of lung disease, aged 60-86 yrs (median 72.0), performed triplets of N 2 MBW using the ExhalyzerD (EcoMedics AG, Duerten, Switzerland) and spirometry. In 296 subjects measurements of RV and TLC were added using body plethysmography (Jaeger, Masterscreen, Care Fusion, Germany). Statistical analysis using IBS SPSS, included simple and multiple regression analyses. Results: Simple regression disclosed moderate relationship between age and RV/TLC (r² 0.33; p 1 /FVC (r² 0.01; p=0.05). While LCI and RV/TLC were moderately associated (r² 0.25; p 1 /FVC was not related to RV/TLC (r² 0.00; n.s.) and weakly to LCI (r² 0.03; p 1 by Conclusion: Peripheral airway ageing is poorly reflected in FEV 1 /FVC ratio, but moderately well described by RV/TLC ratio and LCI.