Functional brain imaging in individuals with chronic cough demonstrates reduced activation in cortical regions associated with voluntary cough suppression. Little is known about the ability of patients with chronic cough to suppress cough. This study aimed to compare the ability to voluntarily suppress cough during inhaled capsaicin challenge in participants with chronic refractory cough with that in healthy controls. In addition, this study aimed to assess the repeatability of capsaicin challenge test with voluntary cough suppression.Participants with chronic refractory cough and healthy controls underwent inhaled capsaicin challenge tests while attempting to suppress their cough responses. After 5 days, either a conventional capsaicin challenge test with no cough suppression attempt, or a repeat test with an attempt at cough suppression was performed. Threshold capsaicin concentrations required to elicit one, two and five coughs were calculated by interpolation. Objective 24-h cough frequency was measured in individuals with chronic refractory cough.Healthy controls were able to suppress capsaicin-evoked cough while participants with chronic refractory cough were not. Geometric mean±sd capsaicin dose thresholds for five coughs with (CS5) and without (C5) suppression attempts were 254.40±3.78 versus 45.89±3.95 µmol·L−1, respectively, in healthy controls (p=0.033) and 3.34±5.04 versus 3.86±5.13 µmol·L−1, respectively, in participants with chronic refractory cough (p=0.922). Capsaicin dose thresholds for triggering five coughs with self-attempted cough suppression were significantly lower in participants with chronic refractory cough than in healthy controls; geometric mean±sd 4.94±4.43 versus 261.10±4.34 µmol·L−1, respectively; mean difference (95% CI) 5.72 (4.54–6.91) doubling doses (p<0.001). Repeatability of cough suppression test in both patients and healthy controls was high; intraclass correlation coefficients of log(CS5) values 0.81 and 0.87, respectively. CS5 was associated with objective cough frequency (ρ=−0.514, p=0.029).Participants with chronic refractory cough were less able to voluntarily suppress capsaicin-evoked cough compared to healthy controls. This may have important implications for the pathophysiology and treatment of chronic cough.

Question: For children with community-acquired pneumonia discharged from an emergency department, observational unit, or inpatient ward (within 48 hours), is subsequent outpatient treatment with oral amoxicillin at a dose of 35-50 mg/kg/day noninferior to 70-90 mg/kg/day, and for 3 days noninferior to 7 days, with regard to the need for antibiotic retreatment? Findings: In this 2x2 factorial randomized clinical trial of 814 children requiring amoxicillin for community-acquired pneumonia at hospital discharge, antibiotic retreatment within 28 days occurred in 12.6% vs 12.4% of those randomized to lower vs higher doses, respectively, and in 12.5% vs 12.5% of those randomized to 3-day vs 7-day amoxicillin duration. Both comparisons met the prespecified 8% noninferiority margin.Meaning: Among children with community-acquired pneumonia discharged from an emergency department, observational unit, or inpatient ward, further outpatient treatment with oral amoxicillin at a dose of 35-50 mg/kg/day was noninferior to a dose of 70-90 mg/kg/day and for 3 days was noninferior to 7 days with regard to the need for later antibiotic retreatment.

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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.

Respiratory symptoms, including cough, are prevalent in individuals with asthma when exercising. This study investigates whether a heat and moisture exchanger (HME) face mask is effective in modulating exercise-induced bronchoconstriction (EIB) and post-exercise cough in a cold, dry environment in individuals with asthma.Twenty-six participants diagnosed with asthma (20 males, 6 females) completed three cycling exercise challenges at 8°C and 24% relative humidity in a randomised order. Participants wore either an HME mask (MASK), sham mask (SHAM), or no mask (CONT). Following a 3-min warm-up, participants completed 6-min cycling at 80% peak power output. Before and after exercise, maximal flow-volume loops were recorded. Post-exercise cough was monitored with a Leicester Cough Monitor (LCM) for 24 h. Results were analysed using repeated-measures ANOVA and Friedman's tests and data were presented as the mean±sd or median (interquartile range (IQR)).Eleven participants failed to demonstrate EIB (i.e. >10% fall in forced expiratory volume in 1 s after exercise) and were removed from analysis. The percentage fall in forced expiratory volume in 1 s following exercise in CONT was greater than MASK (MASK: −6% (7%), SHAM: −11% (11%), CONT: −13% (9%); p<0.01). No difference was found between exercise in cough count per hour over the 24-h monitoring period or the number of coughs in the first hour after exercise.HME masks can attenuate EIB when exercising in cold, dry environments. The SHAM mask may not have been entirely inert, demonstrating the challenges of running randomised control trials utilising control and sham conditions.