Background Chest radiographs are commonly used for the diagnosis of tuberculosis and to assess the extent of disease. A relationship between the extent of disease as determined by smear grade and cavitation has been shown to predict 2-month smear results but little has been done to determine whether radiological severity reflects the bacterial burden at diagnosis. Design/methods Pre-treatment chest X-rays from 1837 subjects with smear positive pulmonary tuberculosis enrolled into the REMoxTB trial were reviewed retrospectively. Two clinicians blinded to clinical details using the Ralph et al scoring system 1 (comprised of the percentage of affected lung field and presence of cavitation) performed separate readings. An independent reader (a radiologist) reviewed discrepant results for quality assessment and cavity presence. The final cavity assessment was combined with the average percentage affected value to give a severity score (maximum score 100% + 40 if any cavitation). The Ralph score was compared to the time to positivity (TTP) of liquid cultures as measured by MGIT 960. The association between CXR severity score and time to positivity (log scale) was evaluated using Spearman's rank correlation coefficient. A Welch t-test was used to compare TTP of those with high and low disease extent and those with and without cavitation. Results Matching sets of data were available for 1422 subjects. The median severity score was 53.75/140 (IQR 32.03-66.25) and median time to culture positivity 117 h (4.88 days). CXR severity score was weakly correlated with time to positivity (Spearman's correlation-0.20, p < 0.0001). Time to positivity was higher in those without cavitation (difference 23.7 h, p < 0.0001) and those with a low area affected (difference 12.1 h, p < 0.0001). Conclusions The radiological severity of pulmonary tuberculosis at diagnosis is weakly correlated with bacterial load as measured by TTP. This suggests that, in addition to bacterial burden, other factors such as immune response influence radiological appearances.

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IntroductionA recent functional MRI study has shown that patients with chronic refractory cough (CRC) have reduced activity in the areas of the brain associated with cough suppression. Cough challenge tests focus only on provoking cough and have limited clinical application due to the wide overlap between healthy subjects and patients with cough. We investigated whether patients with CRC could suppress cough in a cough challenge test.MethodsWe recruited 13 chronic refractory cough patients and 11 healthy controls. Participants underwent an incremental capsaicin challenge test (0.49 to 1000 micromol.L-1) and were instructed “please do not cough during the test”. The concentrations of capsaicin during the cough suppression (CS) protocol required to elicit 1 or more cough (CS1), 2 or more coughs (CS2), and 5 or more coughs (CS5) were documented. Patients with CRC also completed cough-severity and urge-to-cough visual analogue scales (VAS; 0–100 mm), and quality of life, Leicester Cough Questionnaire (LCQ; range 3–21).ResultsPatients with CRC and controls had a mean (SD) age 57 (8) and 51 (7) years and 11 (85%) and 7 (64%) were female, respectively. CRC patients self-reported symptom and health status were; mean (SD) cough severity VAS 58 (31), urge-to-cough VAS 63 (30), and LCQ score 12.1 (4.4). Patients with CRC were less able to suppress cough compared to healthy controls; geometric mean (SD) CS1: 2.30 (3.56) vs 62.46 (5.62), CS2: 2.55 (3.71) vs 70.86 (5.91) and CS5: 3.37 (4.84) vs 321.70 (3.23) micromol.L-1 respectively, all p<0.0001. The mean difference (95% CI) in CS5 between CRC and controls was 6.6 (4.9, 8.3) doubling doses. CS5 was better than CS1 and CS2 at discriminating CRC patients from controls (figure 1). There was no significant association between CS5 and cough severity VAS (correlation coefficient, rs=0.29), urge to cough VAS (rs=0.24) and LCQ (rs=0.32), all p>0.10.ConclusionVoluntary suppression of capsaicin-evoked cough is significantly diminished in chronic refractory cough. Our findings suggest future research should focus on cough inhibitory as well as activation pathways. CS5 has potential to be used as a diagnostic test and to evaluate anti-tussive therapy; this should be investigated further.Abstract S32 Figure 1Cough suppression test. Capsaicin concentration (geometric mean, SD) that provoked 5 or more coughs (CS5) during voluntary suppression of cough.

IntroductionUrge to cough is a conscious perception of the need to cough. We investigated urge-to-cough, triggers and somatic sensations associated with cough in patients with COPD and compared it to patients with chronic refractory cough (CRC).MethodsWe undertook a prospective case-control study of COPD patients with chronic cough (≥8 weeks) and patients with CRC. All patients completed a 27-item structured questionnaire (Cough Hypersensitivity Questionnaire; CHQ), that has a 5-point Likert response scale to assess urge-to-cough, aggravating factors/triggers and somatic sensations (0–4; 0=never and 4=occurs all the time in relation to cough). 10 COPD patients underwent a capsaicin challenge test to provoke an urge-to-cough sensation and to assess cough reflex sensitivity. The concentration of capsaicin that elicited 2 or more coughs (C2) and 5 or more coughs (C5) was recorded.Results62 COPD and 40 CRC patients were recruited (mean(SD) age 64(11) vs 54(14) years, 48% vs 70% females, FEV1% predicted 48.2% (19.0) vs 94.1% (16.6) respectively). The top 5 cough triggers and somatic sensations in patients with COPD and CRC are summarised in Table 1. The severity of sputum trigger of cough and chest sensation associated with cough were significantly greater in COPD compared to CRC; median(IQR) sputum scores: 3 (2–4) vs 2 (1–2) and chest sensation scores: 2 (2–4) vs 1 (0–2) respectively, both p<0.01. The prevalence of urge-to-cough was higher in CRC vs COPD: 97.5% vs 75.8% respectively. The severity of urge to cough and eating/drinking trigger of cough were significantly greater in CRC compared to COPD; median(IQR) urge to cough scores: 3 (2–3) vs 2 (1–3) and eating and drinking scores: 2 (0–3) vs 1 (0–2) respectively, both p=0.02. Geometric mean(SD) C2 and C5 in COPD were 9.5 (18.2) and 10.9 (18.0) micromol.L-1. There was a significant correlation between C5 and urge to cough in COPD (rs=−0.74,p=0.02) but not with sputum trigger score (rs=−0.10,p=0.80).Abstract P103 Table 1Prevalence of triggers and somatic sensations associated with cough in COPD and chronic refractory cough. Data presented as percentage of all patientsTop 5 triggers and somatic sensations associated with coughPrevalence (% patients) COPDSputum87Chest sensation86Smoke or smoky atmosphere81Dry throat77Exercise77Chronic refractory coughUrge to cough98Tickle in throat93Cold air90Irritation in throat88Postural change88ConclusionSputum is a significant self-reported trigger of cough in COPD. In contrast, urge to cough occurs more frequently in CRC. There are likely to be multiple mechanisms of cough in COPD and further studies should investigate whether phenotyping cough on the basis of self-reported triggers and somatic sensations can guide therapy.

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