Mechanical induction of cough in Idiopathic Pulmonary Fibrosis

Abstract

Background: Patients with idiopathic pulmonary fibrosis (IPF) frequently develop a dry, irritating cough which often proves refractory to anti-tussive therapies. The precise pathogenetic mechanisms responsible for this cough are unknown. We hypothesised that changes in nerves modulating mechanical sensitivity in areas of interstitial fibrosis might lead to enhanced cough response to mechanical stimulation of the chest in IPF.

Methods: We studied 27 non-smoking subjects with IPF (63% male), mean (SD) age 71.7 (7) years and 30 healthy non-smokers. Quality of life (Leicester Cough Questionnaire), cough symptom scores and cough severity scores (visual analog scales) were recorded. Percussion stimulation was applied over the posterior lung base, upper anterior chest and manubrium sternum at sequential frequencies (20 Hertz (Hz), 40 Hz and 60 Hz) for up to 60 seconds and repeated twice at two minute intervals. The number of subjects achieving two and five-cough responses, total cough counts and cough latency were recorded. In separate experiments, the effect of mechanical stimulation on the pattern of breathing was determined in eight IPF subjects and five control subjects.

Results: In patients with IPF, we demonstrated strong correlations between subjective cough measurements, particularly the cough symptom score and Leicester Cough Questionnaire (r = -0.86; p < 0.001). Mechanical percussion induced a true cough reflex in 23/27 (85%) IPF subjects, but only 5/30 (17%) controls (p < 0.001). More patients with IPF reached the two-cough response at a lower frequency (20 Hz) posteriorly than at other positions. Highest mean cough totals were seen with stimulation at or above 40 Hz. Mechanical stimulation had no effect on respiratory rate but increased tidal volume in four (50%) subjects with IPF, particularly at higher frequencies. It was associated with increased urge to cough followed by a true cough reflex.

Conclusions: This study demonstrates that patients with IPF show enhanced cough reflex sensitivity to mechanical stimulation of the chest wall whilst normal individuals show little or no response. The observation that low frequency stimulation over the lung base, where fibrosis is most extensive, induces cough in more patients than at other sites supports the hypothesis that lung distortion contributes to the pathogenesis of cough in IPF.

Figures

Figure 1

Study subject undergoing mechanical percussion of the chest using a G5 Variko percussor (Physiotherapie Generale, Casteljaloux, France).

Figure 2

Subjective cough assessment in patients with IPF. a) Relationship between Leicester Cough Questionnaire and VAS scores. b) Relationship between Leicester Cough Questionnaire and cough symptom scores. c) Relationship between VAS and cough symptom scores.

Figure 3

Threshold frequencies at which: a) two-cough responses. b) five-cough responses were induced in each stimulation position in patients with IPF.

Figure 4

Mean (±SEM) total cough count in patients with IPF and controls at different sites of stimulation on the chest wall and at different frequencies.

Figure 5

Reproducibility of mean (±SEM) total cough counts in patients with IPF measured on two occasions one week apart.

Figure 6

Respiratory polygraphy recordings obtained from a subject with IPF demonstrating: a) Increased tidal volume on thoracic and abdominal effort belt recordings following initiation (arrow) of 60 Hz mechanical stimulation to the posterior lung base. b) Increased inspiratory effort on thoracic movement sensors preceding a single true three-phase cough (arrow) during 40 Hz mechanical chest wall stimulation to the posterior lung base.