Cough in Idiopathic Pulmonary Fibrosis

Chronic cough is experienced by most patients with idiopathic pulmonary fibrosis (IPF). It is often the first symptom and is associated with reduced quality of life, increased rates of depression and anxiety, more severe physiological impairment, and disease progression. Although not fully understood, recent gains in understanding the pathophysiology of chronic cough in IPF have been made. The pathophysiology is likely multifactorial and includes alterations in mucous production and clearance, architectural distortion, and increased cough reflex sensitivity, suggesting a role for targeted therapies and multidisciplinary treatment. Modifiable comorbidities can also induce cough in patients with IPF. There is a renewed emphasis on measuring cough in IPF, with clinical trials of novel and repurposed therapies for chronic cough emerging in this population. This review provides an update on the clinical characteristics, pathophysiology, and measurement of chronic cough in patients with IPF and summarizes recent developments in non-pharmacological and pharmacological therapies.

Cough Reflex Sensitivity and Fractional Exhaled Nitric Oxide in Children With Asthma

Individual studies have suggested the utility of fractional exhaled nitric oxide (FeNO) measurement in detecting cough-variant asthma and eosinophilic bronchitis in patients with chronic cough. The aim of this study was to clarify a correlation of cough reflex sensitivity and fractional exhaled nitric oxide in asthmatic children. 25 children with asthma and 15 controls were submitted to cough reflex sensitivity measurement – capsaicin aerosol in doubling concentrations (from 0.61 to 1250 µmol/l) was inhaled by a single breath method. Concentrations of capsaicin causing two (C2) and five coughs (C5) were reported. Fractional exhaled nitric oxide (FeNO) measurement was included. Asthmatic children (11 boys and 14 girls, mean age 9±1 years) and control group (unconfirmed diagnosis of asthma) (6 boys and 9 girls, mean age 8±1 years) were included into the study. FeNO vs. C2 in asthma (Spearman´s rank correlation: -0.146, p=0.49); FENO vs. C5 in asthma (Spearman´s rank correlation: -0.777, p=0.71). We found that there is no correlation between cough reflex sensitivity and fractional exhaled nitric oxide either in children with asthma or in the control group.

Relationship Between Cough Reflex Sensitivity and Body Mass Index in Children With Chronic Cough – a Pilot Study

Obesity is characterized by chronic, low-grade systemic inflammation. Obesity may also be associated with chronic cough. The aim of this pilot study was to clarify relation of cough reflex sensitivity and body mass index (BMI) in children with chronic cough. Altogether 41 children having symptoms of chronic cough were submitted to cough reflex sensitivity measurement. We assessed the relation of cough reflex sensitivity (CKR) due to BMI. Cough reflex sensitivity was defined as the lowest capsaicin concentration which evoked two (C2) or five (C5) coughs. Capsaicin aerosol in doubling concentrations (from 0.61 to 1250 µmol/l) was inhaled by a single breath method (KoKo DigiDoser; nSpire heath Inc, Louisville, CO, USA), modified by the addition of an inspiratory flow regulator valve (RIFR; nSpire heath Inc, Louisville, CO, USA). BMI was calculated. Pulmonary function was within normal range. Concentrations of capsaicin causing two (C2) and five coughs (C5) were reported. Children (22 boys and 19 girls, mean age 6.8 years) cough reflex sensitivity (median, with the Inter-Quartile Range) for C2 was 19.5 (73.4) µmol/l; for C5 it was 78.1 (605.5) µmol/l. We have noticed statistically significant relation of the cough reflex sensitivity (C5) and body mass index (P<0.0001); however, the effect size was small, R2=0.03. Increase of body mass index in one unit is associated with -34.959 µmol/l decrease of C5. We did not find a statistically significant relation between C2 and BMI (P=0.41). The median value of CKR (C2) in boys is not statistically significantly different than the median value of CKR (C2) in girls (P-value 0.5). The median value of CKR (C5) in boys is not statistically significantly different than the median value of CKR (C5) in girls (P-value 0.5). Increase of body mass index in children suffering from chronic cough relates to decrease of cough reflex sensitivity (C5 value).

Cough Hypersensitivity and Suppression in Chronic Obstructive Pulmonary Disease

Cough reflex hypersensitivity (CRH) and impaired cough suppression are features of chronic refractory cough (CRC). Little is known about cough suppression and CRH in cough associated with chronic obstructive pulmonary disease (COPD). This study investigated the ability of participants with COPD to suppress cough during a cough challenge test in comparison to participants with CRC and healthy subjects. This study also investigated whether CRH is associated with chronic cough in COPD.Participants with COPD (n=27), CRC (n=11), and healthy subjects (n=13) underwent capsaicin challenge test with and without attempts to self-suppress cough in a randomised order over 2 visits, 5 days apart. For participants with COPD, the presence of self-reported chronic cough was documented, and objective 24-h cough frequency was measured.Amongst participants with COPD, those with chronic cough (n=16) demonstrated heightened cough reflex sensitivity (CRS) compared to those without chronic cough (n=11); geometric mean (sd) capsaicin dose thresholds for 5 coughs (C5) 3.36 (6.88) versus 44.50 (5.90) µmol·L−1 respectively (p=0.003). Participants with CRC also had heightened CRS compared to healthy participants; geometric mean (sd) C5 3.86 (5.13) versus 45.89 (3.95) µmol·L−1 respectively (p<0.001). Participants with COPD were able to suppress capsaicin-evoked cough, regardless of the presence or absence of chronic cough; geometric mean (sd) capsaicin dose thresholds for 5 coughs without self-suppression attempts (C5) and with (CS5) were 3.36 (6.88) versus 12.80 (8.33) µmol·L−1 (p<0.001) and 44.50 (5.90) versus 183.2 (6.37) µmol·L−1 (p=0.006) respectively. This was also the case for healthy participants (C5 versus CS5: 45.89 (3.95) versus 254.40 (3.78) µmol·L−1, p=0.033), but not those with CRC, who were unable to suppress capsaicin-evoked cough (C5 versus CS5: 3.86 (5.13) versus 3.34 (5.04) µmol·L−1, p=0.922). C5 and CS5 were associated with objective 24-h cough frequency in participants with COPD; ρ=−0.430, p=0.036 and ρ=−0.420, p=0.041 respectively.Participants with COPD-chronic cough and CRC both have heightened cough reflex sensitivity but in contrast, only participants with CRC were unable to suppress capsaicin evoked cough. This suggests differing mechanisms of cough between participants with COPD and CRC, and the need for disease specific approaches to its management.

Cough Reflex Sensitivity in Asthmatic Children

New knowledge about the neural aspects of cough has revealed a complex network of pathways that initiate cough. The effect of inflammation on cough neural processing occurs at multiple peripheral and central sites within the nervous system. Evidence exists that direct or indirect neuroimmune interaction induces a complex response, which can be altered by mediators released by the sensory or parasympathetic neurons and vice versa. The aim of this study was to clarify changes of cough reflex sensitivity – the activity of airway afferent nerve endings - in asthmatic children. 25 children with asthma and 15 controls were submitted to cough reflex sensitivity measurement - capsaicin aerosol in doubling concentrations (from 0.61 to 1250 µmol/l) was inhaled by a single breath method. Concentrations of capsaicin causing two (C2) and five coughs (C5) were reported. Asthmatic children' (11 boys and 14 girls, mean age 9 ± 1 yrs) cough reflex sensitivity (geometric mean, with the 95 % CI) for C2 was 4.25 (2.25-8.03) µmol/l vs. control C2 (6 boys and 9 girls, mean age 8 ± 1 yrs) was 10.61 (5.28-21.32) µmol/l (p=0.024). Asthmatic children' C5 was 100.27 (49.30-203.93) µmol/l vs. control C5 56.53 (19.69-162.35) µmol/l (p=0.348). There was a statistically significant decrease of C2 (cough threshold) in the asthmatic patients relative to controls (p-value for the two-sample t-test of log(C2) for the one-sided alternative, p-value = 0.024). The 95 % confidence interval for the difference of the mean C2 in asthma vs. control, [1.004, 6.207]. For C5, the difference was not statistically significant (p-value = 0.348). There was a statistically significant decrease of cough reflex sensitivity (the activity of airway afferent nerve endings) - C2 value in the asthmatic children relative to controls.

Hustenreflex bei Demenz: Differenzierte Medikamentenstrategie zur Vermeidung von Pneumonien nutzen

Cough, an important respiratory symptom, predominantly involves the brainstem and the urge-to-cough (UTC) is modulated by the cerebral cortex. Lewy body disease is associated with decreased cough reflex sensitivity and central respiratory chemosensitivity. Additionally, the insula, associated with the UTC, shows decreased activation and atrophy in dementia with Lewy bodies (DLB). We investigated the relationships between cognition and cough reflex and the UTC and compared the differences in responses of patients with DLB and other dementia subtypes. We conducted a cross-sectional study within a geriatric ward of a university hospital involving elderly patients diagnosed with Alzheimer’s disease (AD), DLB, or non-dementia (controls). The cough reflex sensitivities were estimated based on the lowest concentrations of inhaled citric acid that could induce ≥2 coughs (C2) or ≥5 coughs (C5). Subjects were asked to rate the UTC based on the threshold concentrations (Cu) using the modified Borg scale. C2, C5 and Cu were negatively correlated with cognitive function in female participants but not in males (p < 0.01). The cough reflex sensitivities expressed as C2 and C5 were significantly higher in the DLB group than in the AD and control groups (p < 0.01 adjusted for gender). The UTC threshold expressed as Cu was also significantly higher in the DLB group, while the UTC log-log slope was less responsive in the DLB group than in the other groups. The cough reflex sensitivity and perceived UTC deteriorated in the DLB group more than in the other groups. This result might be valuable in treating patients with DLB.