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A5836 - Persistent Airflow Limitation, Lung Elastic Recoil and Inflammation in Older Non-Smokers with Asthma
Author Block: K. Tonga1, C. S. Farah2, C. Thamrin3, F. Tang4, J. Santos5, P. Sharma6, B. Oliver7, G. King8; 1Airway Physiology and Imaging Group, Woolcock Institute of Medical Research, Sydney, Australia, 2Respiratory Medicine, Concord Hospital, Sydney, Australia, 3Airway Physiology and Imaging, Woolcock Institute of Medical Research, Sydney, Australia, 4Woolcock Institute of Medical Research, Sydney, Australia, 5School of Life Sciences, University of Technology, Sydney, Australia, 6University of Technology, Sydney, Australia, 7Cell Biology, Woolcock Institute of Medical Research, Sydney, Australia, 8Royal North Shore Hospital, Sydney, Australia.
Rationale:
Persistent airflow limitation (PAL) can develop in older non-smokers with asthma however the mechanism is unknown. Loss of lung elastic recoil may contribute as this occurs with aging and may occur in asthma as a result of changes in lung tissue fibres or surface tension properties. These changes may in turn be due to neutrophilic inflammation as this is more common in older people with asthma. TH17 cells have been linked to neutrophilic inflammation, with increased concentrations of IL-17 (predominant product of TH17 cells) reported in sputum of asthma patients. IL-17A and IL-17F have also been linked to neutrophilic inflammation and steroid resistance. We aimed to determine the relationship between airflow limitation, lung elastic recoil and airway inflammation. We hypothesize that neutrophilic inflammation is associated with reduced lung elastic recoil, and that both relate to PAL in older non-smoking asthmatics.
Methods:
Non-smoking adults with asthma were treated with standardised high-dose inhaled corticosteroid/long-acting beta-agonist for two months to eliminate eosinophilic inflammation. Subjects underwent standard lung function and lung elastic recoil measurement using an oesophageal balloon to construct the pressure-volume (P-V) curve. An exponential fit to the P-V curve, V=A-Bexp(-KP) (Colebatch method), was used to derive K, a measure of compliance. Increased K indicates loss of lung elastic recoil. Subsequently bronchoscopy was performed to obtain bronchoalveolar lavage fluid (BAL) for differential leukocyte count and IL-17 cytokine measurement (using multiplex immunoassay). Spearman correlations were assessed.
Results:
Nineteen subjects (11 male; mean±SD age 63±9 years, asthma duration 38±22 years) demonstrated moderate PAL (mean±SD z-score) (post-bronchodilator FEV1 -2.05±0.75, FVC -0.61±0.95, FEV1/FVC -2.46±0.90). Reduced lung elastic recoil was demonstrated in 9/18 subjects ((median(IQR)z-score) K 1.57(-1.08–3.43)). FEV1/FVC z-score correlated negatively with age (r=-0.49,p=0.03) and K (r=-0.53,p=0.023). Neutrophilic airway inflammation was not demonstrated (mean±SD: neutrophils 9.1±18.1%, n=10). Mean±SD IL-17A and IL-17F was 116.0±113.4pg/ml and 13.4±13.2pg/ml (n=17). FEV1/FVC and K did not correlate with BAL neutrophil count or IL-17 cytokines.
Conclusion:
Loss of lung elastic recoil relates to PAL in older non-smokers with asthma, suggesting a role for lung tissue changes in addition to airway remodeling. Older age plays an additional detrimental role to the disease process. Small numbers in this cohort may account for the lack of neutrophilic airway inflammation. Despite no relationship with neutrophilic airway inflammation in this exploratory study, the underlying cellular mechanisms require further investigation. An alternate paradigm of ‘lung remodeling’ may have potential implications on preventing PAL in this population.