Clinical and pulmonary function changes in cough variant asthma with small airway disease

Abstract

Background: It is known that small airway disease is present across all asthma severities; however, its prevalence and clinical characteristics in cough variant asthma (CVA) have not been fully illuminated.

Methods: A total of 77 CVA patients with preserved proximal airway function (FEV1/FVC > 70%) were enrolled in this study. The correlation between forced expiratory flow at 50% (FEF_50%) and FEF_25-75% in the CVA population was first evaluated. FEF_50% was determined to be an easy and feasible parameter for identifying small airway disease. CVA with small airway disease is defined as FEF_50% < 70%, whereas CVA with normal small airways is identified as FEF_50% > 70%. Demographic features, clinical characteristics, lung function and induced sputum test results were determined at the initial visit and at the final visit 1 year later.

Results: FEF_50% is a good marker for small airway disease. The cutoff value of 70% is more sensitive than the previously published 60% for identifying more patients with small airway problems early. Nearly half of the CVA population (45.4%) in our cohort had small airway disease. In both group, symptoms improved greatly after anti-asthmatic treatment. Interestingly, the changes in symptom scores [Asthma Control Test (ACT) and ACQ] were even greater in the CVA with small airway disease group than in the control group because of the higher medication usage in this subpopulation in real life. However anti-asthmatic therapy can not reverse small airway dysfunction. At last visit, FEF_50% of CVA with small airway diseases was 57.2% ± 10.5%, still much lower than the control group (FEF_50% = 92.6% ± 16.5%).

Conclusions: In our cohort, nearly half of the CVA population had small airway disease. Their demographic features, clinical characteristics, airway eosinophils and drug responsiveness were quite similar between two groups, which means these indices can not be used as markers to identify small airway obstruction. We found FEF_50% is an easy and feasible marker for early identification. Regular anti-asthmatic medication helped to improve clinical scores in patients with small airway disease, but the obstruction could not be reversed over 1-year period.

Keywords: Cough variant asthma; Forced expiratory flow at 50% (FEF50%); Small airway disease.

Fig. 1

Patients screen and follow up. 250 subjects were screened and 173 subjects were excluded for wrong phone number, no will to attend the trial or age limitation. 77 initially diagnosed CVA patients were enrolled. Participants were divided into two groups: CVA with lower FEF50%, CVA with normal FEF50%. Twenty participants were dropped out during follow up. A total of 57 patients complete the observation over a year

Fig. 2

FEF50% and FEF25–75% as early markers of small airway disease. a Representative spirometry results in our cohort are showed. Normal airway is the group CVA with normal FEF50%. Small airway disease is the group CVA with lower FEF50%. b Diagnostic test of FEF50%. FEF25–75% is defined as gold standard and FEF25–75% < 70% predicted is set as cut value. The sensitivity, specificity and accuracy of new measurement (FEF50%) are measured. c The average value of FEF50% and FEF25–75% (p > 0.05). The linear correlation analysis of FEF50% and FEF25–75% in CVA patients. All spirometries were performed by well-trained technician with all data repeated three times

Fig. 3

Asthma clinical control over a year by ACT and ACQ questionnaire. Both ACT and ACQ score improved in both groups when compared final visit with initial visit. The scale of improvement in CVA with lower FEF50% is much greater than the control groups

Fig. 4

Medication usage for CVA cohort in real-life world. The application timing of medication usage in lower FEF50% group (a) and normal FEF50% group (b). c The rate of bronchodilators usage in the two groups. d The rate of ICS usage in the two groups. p < 0.05: statistically significant

Fig. 5

Recurrence of CVA over a year. The recurrence rate in CVA with FEF50% lower group is higher than that of control group (p < 0.05: statistically significant)

Fig. 6

Changes of lung function test between groups over a year. a FEV1/FVC at the first visit (V1) and final visit (12 months later) (V2) for lower FEF50% group and normal FEF50% group. b FEV1% at the first visit (V1) and final visit (12 months later) (V2) for lower FEF50% group and normal FEF50% group. c FEF50% at the first visit (V1) and final visit (12 months later) (V2) for lower FEF50% group and normal FEF50% group. p < 0.05: statistically significant