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The widespread use of cough counting tools has, to date, been limited by a reliance on human input to determine cough frequency. However, over the last two decades advances in digital technology and audio capture have reduced this dependence. As a result, cough frequency is increasingly recognised as a measurable parameter of respiratory disease. Cough frequency is now the gold standard primary endpoint for trials of new treatments for chronic cough, has been investigated as a marker of infectiousness in tuberculosis (TB), and used to demonstrate recovery in exacerbations of chronic obstructive pulmonary disease (COPD). This review discusses the principles of automatic cough detection and summarises key currently and recently used cough counting technology in clinical research. It additionally makes some predictions on future directions in the field based on recent developments. It seems likely that newer approaches to signal processing, the adoption of techniques from automatic speech recognition, and the widespread ownership of mobile devices will help drive forward the development of real-time fully automated ambulatory cough frequency monitoring over the coming years. These changes should allow cough counting systems to transition from their current status as a niche research tool in chronic cough to a much more widely applicable method for assessing, investigating and understanding respiratory disease.

P57 Figure 1Cough severity analogue scale (a) and cough-specific health status LCQ (b) ranges for Pateint Global Impression of Severity categories[Figure omitted. See PDF]ConclusionThe PGI-S scale is a simple tool that characterises cough severity in a format familiar to clinicians, and allows comparisons with other conditions. The PGI-S has a strong relation with validated cough measures such as VAS and LCQ. Future studies should investigate the reproducibility and clinically important threshold for change of the PGI-S.

Objectives The primary objective of MATIS is to determine the efficacy of ruxolitinib (RUX) or fostamatinib (FOS) compared to standard of care (SOC) with respect to reducing the proportion of hospitalised patients progressing from mild or moderate to severe COVID-19 pneumonia. Secondary objectives, at 14 and 28 days, are to: Determine the efficacy of RUX or FOS to reduce mortality Determine the efficacy of RUX or FOS to reduce the need for invasive ventilation or ECMO Determine the efficacy of RUX or FOS to reduce the need for non-invasive ventilation Determine the efficacy of RUX or FOS to reduce the proportion of participants suffering significant oxygen desaturation Determine the efficacy of RUX or FOS to reduce the need for renal replacement therapy Determine the efficacy of RUX and FOS to reduce the incidence of venous thromboembolism Determine the efficacy of RUX and FOS to reduce the severity of COVID-19 pneumonia [graded by a 9-point modified WHO Ordinal Scale* Determine the efficacy of RUX or FOS to reduce systemic inflammation Determine the efficacy of RUX or FOS to the incidence of renal impairment Determine the efficacy of RUX or FOS to reduce duration of hospital stay Evaluate the safety of RUX and FOS for treatment of COVID-19 pneumonia. Trial design A multi-arm, multi-stage (3-arm parallel-group, 2-stage) randomised controlled trial that allocates participants 1:1:1 and tests for superiority in experimental arms versus standard of care. Participants Patients will be recruited while inpatients during hospitalisation for COVID-19 in multiple centres throughout the UK including Imperial College Healthcare NHS Trust. INCLUSION: Patients age ≥ 18 years at screening Patients with mild or moderate COVID-19 pneumonia, defined as Grade 3 or 4 severity by the WHO COVID-19 Ordinal Scale Patients meeting criteria: Hospitalization AND SARS-CoV2 infection (clinically suspected or laboratory confirmed) AND Radiological change consistent with COVID-19 disease CRP ≥ 30mg/L at any time point Informed consent from patient or personal or professional representative Agreement to abstain from sexual intercourse or use contraception that is >99% effective for all participants of childbearing potential for 42 days after the last dose of study drug. For male participants, agreement to abstain from sperm donation for 42 days after the last dose of study drug. EXCLUSION: Requiring either invasive or non-invasive ventilation including CPAP or high flow nasal oxygen at any point after hospital admission but before baseline, not related to a pre-existing condition (e.g., obstructive sleep apnoea) Grade ≥ 5 severity on the modified WHO COVID-19 Ordinal Scale, i.e. SpO2 < 90% on ≥ 60% inspired oxygen by facemask at baseline; non-invasive ventilation; or invasive mechanical ventilation In the opinion of the investigator, progression to death is inevitable within the next 24 hours, irrespective of the provision of therapy Known severe allergic reactions to the investigational agents Child-Pugh B or C grade hepatic dysfunction Use of drugs within the preceding 14 days that are known to interact with any study treatment (FOS or RUX), as listed in the Summary of Product Characteristics Pregnant or breastfeeding Any medical condition or concomitant medication that in the opinion of the investigator would compromise subjects’ safety or compliance with study procedures. Any medical condition which in the opinion of the principal investigator would compromise the scientific integrity of the study Non-English speakers will be able to join the study. If participants are unable to understand verbal or written information in English, then hospital translation services will be requested at the participating site for the participant where possible. Intervention and comparator RUXOLITINIB (RUX) (14 days): An oral selective and potent inhibitor of Janus Associated Kinases (JAK1 and JAK2) and cell proliferation (Verstovek, 2010). It is approved for the treatment of disease-related splenomegaly or constitutional symptoms in myelofibrosis, polycythaemia vera and graft-versus-host-disease. RUX will be administered orally 10mg bd Day 1-7 and 5mg bd Day 8-14. FOSTAMATINIB (FOS) (14 days): An oral spleen tyrosine kinase inhibitor approved for the treatment of thrombocytopenia in adult participants with chronic immune thrombocytopenia. FOS will be administered orally 150mg bd Day 1-7 and 100mg bd Day 8-14. Please see protocol for recommended dose modifications where required. COMPARATOR (Standard of Care, SOC): experimental arms will be compared to participants receiving standard of care. It is accepted that SOC may change during a rapidly evolving pandemic. Co-enrolment to other trials and rescue therapy, either pre- or post-randomisation, is permitted and will be accounted for in the statistical analysis. Main outcomes Pairwise comparison (RUX vs SOC and FOS vs SOC) of the proportion of participants diagnosed with severe COVID-19 pneumonia within 14 days. Severe COVID-19 pneumonia is defined by a score ≥ 5 on a modified WHO COVID-19 Ordinal Scale, comprising the following indicators of disease severity: Death OR Requirement for invasive ventilation OR Requirement for non-invasive ventilation including CPAP or high flow oxygen OR O2 saturation < 90% on ≥60% inspired oxygen Randomisation Participants will be allocated to interventions using a central web-based randomisation service that generates random sequences using random permuted blocks (1:1:1), with stratification by age ( Blinding (masking) No participants or caregivers are blinded to group assignment. Clinical outcomes will be compared blind to group assignment. Numbers to be randomised (sample size) For an early informal dose examination by the Data Monitoring Committee a minimum of 30 participants will be recruited. For Stage 1 of this multi-arm multi-stage study, 171 participants will be randomised, with 57 participants in each arm. If at least one experimental intervention shows promise, then Stage 2 will recruit a further 95 participants per arm. Sample size calculations are given in the protocol. Trial Status Recruitment is ongoing and started 2nd October 2020. We anticipate completion of Stage 1 by July 2021 and Stage 2 by April 2022. The current protocol version 2.0 of 11th February 2021 is appended. Trial registration EudraCT: 2020-001750-22, 9th July 2020 ClinicalTrials.gov: NCT04581954, 9th October 2020 Full protocol The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expediting dissemination of this material, familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Chronic cough is a common reason for medical consultation, and effective assessment is essential for management. A routine clinical assessment should include history, examination, a chest radiograph and spirometry as a minimum. Further investigations should be guided by the presenting features, comorbidities, and previous investigation results and responses to treatment trials. These investigations, including oesophageal manometry, are often used to assess specific aetiologies. Assessments of cough severity and impact should also be used, and repeated over time, particularly in response to treatment trials. It is not uncommon to fail to identify the ultimate underlying cause of chronic cough. The desire of both the patient and the clinician to identify the aetiology will guide investigations to some extent, although it is important to avoid over-investigation beyond the current evidence base and guidelines.

Cough reflex hypersensitivity and impaired cough suppression are features of chronic refractory cough (CRC). Little is known about cough suppression and cough reflex hypersensitivity in cough associated with chronic obstructive pulmonary disease (COPD). This study investigated the ability of patients with COPD to suppress cough during a cough challenge test in comparison to patients with CRC and healthy subjects. This study also investigated whether cough reflex hypersensitivity is associated with chronic cough in COPD.Participants with COPD (n=27) and CRC (n=11) and healthy subjects (n=13) underwent capsaicin challenge tests with and without attempts to self-suppress cough in a randomised order over two visits, 5 days apart. For patients with COPD, the presence of self-reported chronic cough was documented, and objective 24-h cough frequency was measured.Amongst patients with COPD, those with chronic cough (n=16) demonstrated heightened cough reflex sensitivity compared to those without chronic cough (n=11): geometric mean±sdcapsaicin dose thresholds for five coughs (C5) 3.36±6.88 µmol·L−1versus44.50±5.90 µmol·L−1, respectively (p=0.003). Participants with CRC also had heightened cough reflex sensitivity compared to healthy participants: geometric mean±sdC5 3.86±5.13 µmol·L−1versus45.89±3.95 µmol·L−1, respectively (psdcapsaicin dose thresholds for 5 coughs without self-suppression attempts (C5) and with (CS5) were 3.36±6.88 µmol·L−1versus12.80±8.33 µmol·L−1(p−1versus183.2±6.37 µmol·L−1(p=0.006), respectively. This was also the case for healthy participants (C5versusCS5: 45.89±3.95 µmol·L−1versus254.40±3.78 µmol·L−1, p=0.033), but not those with CRC, who were unable to suppress capsaicin-evoked cough (C5versusCS5: 3.86±5.13 µmol·L−1versus3.34±5.04 µmol·L−1, p=0.922). C5 and CS5 were associated with objective 24-h cough frequency in patients with COPD: ρ= −0.430, p=0.036 and ρ= −0.420, p=0.041, respectively.Patients with COPD-chronic cough and CRC both had heightened cough reflex sensitivity but only patients with CRC were unable to suppress capsaicin-evoked cough. This suggests differing mechanisms of cough between patients with COPD and CRC, and the need for disease-specific approaches to its management.

Background Cough is predictive of exacerbations of chronic obstructive pulmonary disease (COPD). Little is known about cough reflex sensitivity during exacerbation of COPD and whether it is associated with exacerbation frequency. This pilot study aimed to investigate cough reflex sensitivity during and following recovery from exacerbation of COPD, and its association with the frequency of future exacerbations. In addition, the repeatability of cough reflex sensitivity in stable COPD was investigated. Methods Twenty participants hospitalised with exacerbation of COPD underwent inhaled capsaicin challenge during exacerbation and after 6 weeks of recovery. The frequency of future exacerbations was monitored for 12 months. The repeatability of cough reflex sensitivity was assessed in separate participants with stable COPD, who underwent 2 capsaicin challenge tests, 6 weeks apart. Results Cough reflex sensitivity was heightened during exacerbation of COPD. Geometric mean (SD) capsaicin concentration thresholds to elicit 5 coughs (C5) during exacerbation and after 6 weeks of recovery were 1.76 (3.73) vs. 8.09 (6.25) μmol L−1, respectively (p ρ = − 0.687, p = 0.003). C5 was highly repeatable over 6 weeks in stable COPD, and intraclass correlation coefficient was 0.85. Conclusion Cough reflex sensitivity is heightened during exacerbation of COPD and reduces after recovery. The persistence of cough reflex hypersensitivity at recovery was associated with the frequency of future exacerbations.

SETTING Although cough in tuberculosis (TB) is presumed to be important for transmission, there is little objective supporting evidence. OBJECTIVE To describe 24-h cough frequency in a group with TB, and investigate associations with household rates of infection. DESIGN Patients with a new diagnosis of pulmonary TB underwent 24-h cough frequency measurement at or just before initiation of anti-tuberculosis treatment. A group with latent Mycobacterium tuberculosis infection (LTBI) acted as controls. Rates of infection among household contacts of sputum smear-positive TB were measured using the interferon-gamma release assay and the tuberculin skin test, and compared with variables relating to the contacts themselves, and to the index case, including cough frequency. RESULTS Daily cough frequency in TB patients (n = 44) was variable (geometric mean [GM] 174, interquartile range [IQR] 68-475 coughs/24 h), higher than in LTBI (n = 17; GM 19 coughs/24 h, IQR 8-53; P < 0.001), and higher during the day than overnight (GM 8.9 coughs/h, IQR 4.1-19.0 vs. GM 2.9 coughs/h, IQR 0.7-13.4; P < 0.0001). Also, 24-h cough frequency in TB was associated with sputum smear status (P = 0.040), but not smoking (P = 0.475). Multivariable logistic regression confirmed that infection in contacts was independently associated with index case sputum smear grade (P = 0.014) and cough frequency (P = 0.022). CONCLUSION Measurement of 24-h cough frequency in pulmonary TB helps predict infectiousness and transmission patterns.

Introduction Cough leads to increased intra-abdominal pressure, thus chronic cough may increase the risk of stress urinary incontinence. We investigated the prevalence, duration and frequency of urinary incontinence in female patients with chronic cough. Methods Consecutive female patients with chronic cough were recruited from a tertiary specialist cough clinic. Participants self-completed a structured questionnaire to record demographics, anthropometrics, duration of cough, and presence, duration and frequency of urinary incontinence. Results 71 participants; mean (SD) age 57.0 (14.0) years, median (IQR) BMI 26.9 (23.1–33.4) kg·m-2 and duration of cough 6 (3–15) years; were recruited. 40 (56%) participants reported urinary incontinence; median (IQR) duration 4.0 (3.0–6.5) years. The frequency of urinary incontinence episodes was daily, 1–6 times weekly and less than once a week in 18 (45%), 8 (20%) and 12 (30%) patients respectively. 28 of 40 (70%) participants reported that urinary incontinence only occurred after coughing, thus had stress incontinence. 18 of 40 (45%) participants reported their onset of urinary incontinence followed the onset of chronic cough. There was no significant difference in age (p=0.742), BMI (p=0.907) and duration of cough (p=0.964) between patients with and without urinary incontinence. Discussion Urinary incontinence affects over half of female patients with chronic cough. Further studies should investigate the characteristics of urinary incontinence in a larger population (stress vs irritable bladder). There is also a pressing need to develop clinical management protocols for cough related incontinence.

Introduction: Increased cough is common in chronic obstructive pulmonary disease exacerbations (ECOPDs). We hypothesised that cough reflex sensitivity (CRS) is increased during ECOPD, and that CRS is associated with future ECOPD risk. Methods: Patients hospitalised with ECOPD underwent inhaled capsaicin challenges to determine threshold concentrations required to elicit 5 coughs (C5) during admission (TE) and after a 6-week recovery period (TR). Spirometry, cough severity visual analogue scale (VAS) rating, and the COPD Assessment Test (CAT) were completed. In the following 12 months, the number of moderate and severe ECOPDs were recorded (requiring medication change and/or hospital admission, separated by ≥14 days) (Seemungal et al 2000). Results: 16 patients were recruited: mean (SD) age 67 (6.6) years, 9 (56%) female, FEV1 34.6 (10.1) % predicted. C5 was significantly lower at TE than at TR; geometric mean (SD) 1.64 (3.84) vs. 8.94 (6.50) μmol⋅L-1; mean (95% CI) doubling dose difference in C5: 2.46 (0.93-3.57), p Discussion: Cough reflex sensitivity was heightened during ECOPD, and the change in C5 at 6 weeks was associated with exacerbation frequency in the following 12 months. These novel observations require further study.

Introduction: Inflammation-mediated sensory sensitisation may increase breathlessness intensity relative to neural respiratory drive (NRD) during ECOPD. We hypothesised that breathlessness intensity is higher relative to NRD during ECOPD than at recovery. Methods: Patients hospitalised with ECOPD underwent the incremental shuttle walk test (ISWT) during admission (TE) and 6 weeks after (TR). Parasternal intercostal muscle electromyogram (EMGpara) was recorded continuously for 10 minutes during ISWT recovery. Modified Borg breathlessness intensity (mBorgBI) was recorded every minute. Neural respiratory drive index (NRDI) was the product of EMGpara%max and respiratory rate. NRDI-mBorgBI relationships were analysed with linear mixed effects model. Results: 13 patients; median (IQR) age 67 (61-73) years, 7 (54%) female, FEV1 27 (25-42)% predicted, length of stay 5 (3-7) days; were recruited. mBorgBI was closely related to NRDI (s=0.005, p Discussion: Absence of significant intra-individual differences in NRDI-mBorgBI relationships between ECOPD and 6 weeks after suggests that inflammation does not influence breathlessness perception relative to NRD during ECOPD. This emphasises the importance of strategies that improve respiratory mechanics during ECOPD.

New evidence from tussive challenges and the P2X inhibitor gefapixant strengthens ATP as a driver of chronic cough. Cough responses to other irritants probably involve a separate peripheral activation pathway. Hypersensitivity may be due to distinct processes again.http://bit.ly/2YR6MuZ

The accurate and consistent assessment of cough is essential not only for optimum standards of clinical care but also to drive forward advances in our understanding of cough. A range of tools for the subjective and objective measurement of cough exists, and their ongoing development has coincided with growth in clinical and preclinical research in cough, resulting in novel findings and promising new treatments. The most widely used and most fruitful approaches to assessing cough are discussed, along with some newer and preliminary techniques and directions for the future. These include methods for measuring cough-specific quality of life, subjective severity, cough frequency, intensity, and sensitivity of the underlying cough reflex. Ongoing development and more widespread adoption of cough assessment tools should help describe the heterogeneity of cough phenotypes, and may better guide treatment by enabling prediction of responses to pharmacological and nonpharmacological antitussive therapies. More detailed assessments of cough may also bring benefits in measuring the transmission of respiratory infections, or in managing reduced airway protection in neuromuscular disease. Population-wide assessments should also help understand the epidemiology of cough and assist in screening for disease.

Introduction Acute cough is a common symptom of upper respiratory tract infections (URTI); a condition with a high health economic impact. There is currently no validated acute cough symptom severity assessment tool. A preliminary Acute Cough Scale (ACS) was developed following focus groups and semi-structured interviews with patients and healthcare professionals. We investigated the internal consistency, responsiveness and concurrent validity of the ACS in a preliminary study. Methods Participants with URTI of onset Results 28 participants were recruited; mean (SD) age 36.0 (20.0) years, 18 (64%) females. The preliminary ACS items regarding anxiousness and vomiting were removed secondary to floor effects (>60% of responses at minimum response); no significant ceiling effects were observed. The refined ACS consisted of 12 items; none of which had an inter-item correlation >0.8. Internal consistency was high after item reduction: Cronbach’s a=0.892. The ACS was able to identify a significant difference in symptom severity between days 1 and 7: mean (SD) ACS scores 19.8 (11.0) vs 12.2 (12.3), p=0.009 (figure 1). The ACS scores on days 1 and 7 were associated with VAS; r=0.553 (p=0.002), r=0.881 (p Discussion The preliminary results show that the ACS has good internal consistency and is able to detect changes in acute cough symptom severity over 7 days. The ACS has good concurrent validity when compared to the VAS and LCQ-Acute. Further studies in larger populations using psychometric methodology are needed to optimise the measurement characteristics of the ACS.

Introduction Increased breathlessness is a cardinal symptom of acute exacerbations of chronic obstructive pulmonary disease (AECOPD). Breathlessness intensity is closely related to neural respiratory drive (NRD). However, it has been proposed that airway inflammation, leading to sensitisation of pulmonary C-fibres, may increase breathlessness intensity relative to NRD during AECOPD. We hypothesised that breathlessness intensity, relative to NRD, would be higher during AECOPD than when clinically stable. Methods Patients hospitalised with a clinician diagnosis of AECOPD were studied during admission (TAECOPD) and after a 6 week recovery period (TREC). On both occasions, patients underwent incremental shuttle walk testing to their symptom-limited maximum. Parasternal intercostal muscle electromyogram (EMGpara) recordings were made continuously over the subsequent 10 min recovery period. Modified Borg (mBorg) breathlessness intensity was recorded at each one-minute interval. EMGpara, expressed as a proportion of peak inspiratory EMGpara recorded during maximal volitional manoeuvres (EMGpara%max), was multiplied by respiratory rate to calculate the NRD index (NRDI). NRDI-breathlessness intensity relationships were analysed by applying linear mixed effects model analysis. Results 12 patients (median (IQR) age 67.5 (55.0–72.8) years, 6 (50%) female, mMRC 3 (2–3), FEV141.0 (31.0–56.8)% predicted, length of stay 6 (3–8) days) were recruited. mBorg breathlessness intensity was closely related to NRDI (beta=0.006, p Discussion Contrary to our hypothesis, we observed no significant differences in the relationship between NRD and breathlessness intensity in COPD patients during an AECOPD when compared to the stable state. This suggests that airway inflammation does not influence the key association between NRD and breathlessness during AECOPD. This emphasises the importance of treatment strategies that reduce the load on the respiratory muscle pump and ventilatory drive to the management of breathlessness in AECOPD.

The BMJ ’s article about aerosol transmission in covid-19 rightly draws attention to an important subject, but the title—“Risk of aerosol transmission to staff outside of intensive care is likely to be higher than predicted”—is misleading.1 The risk of aerosol transmission is probably substantial in covid-19, and infection control policies should reflect this. But the quoted study does not help us quantify this risk outside of intensive care units. The study of Hamilton and colleagues, to which the article refers, reports two …

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 (pParticipants 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.

Cough is a prominent symptom of pulmonary tuberculosis (TB), one of the oldest and most prevalent infectious diseases. Coughing probably has a pivotal role in transmission of the causative organism Mycobacterium tuberculosis. Despite this, little research to date has addressed this subject. Current knowledge of the mechanisms of cough in TB and how exactly coughing patterns predict infectiousness is scant, but this is changing. This overview summarises the existing evidence for the infectiousness of cough in TB, clinical correlates, and possible causes of cough in TB. Potential unique characteristics of cough in the disease are discussed, as is treatment and the subjective awareness of coughing in the disease.

Introduction Urge 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). Methods We 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. Results 62 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 Conclusion Sputum 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.

Introduction A 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. Methods We 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). Results Patients 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 0.10. Conclusion Voluntary 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.

The transmission of tuberculosis is complex. Necessary factors include a source case with respiratory disease that has developed sufficiently for Mycobacterium tuberculosis to be present in the airways. Viable bacilli must then be released as an aerosol via the respiratory tract of the source case. This is presumed to occur predominantly by coughing but may also happen by other means. Airborne bacilli must be capable of surviving in the external environment before inhalation into a new potential host—steps influenced by ambient conditions and crowding and by M. tuberculosis itself. Innate and adaptive host defenses will then influence whether new infection results; a process that is difficult to study owing to a paucity of animal models and an inability to measure infection directly. This review offers an overview of these steps and highlights the many gaps in knowledge that remain.

Introduction: EuroQol Five Dimensions Five Level questionnaire (EQ-5D-5L) can be used to assess generic health status and cost-utility. We investigated EQ-5D-5L health status in chronic cough and performed a systematic review of the literature in other respiratory diseases. Method: Prospective study of patients with chronic cough from a specialist clinic who completed EQ-5D (range -0.594 to 1; high score = better health), cough severity visual analogue scale (VAS) and Leicester Cough Questionnaire (LCQ). Systematic review of literature was conducted for studies of EQ-5D-5L in other respiratory diseases. Results: 101 patients had chronic cough of mean (SD) duration 9 (8) months; mean age 53 (14) years; 68% female. Associated diagnoses included asthma (20%), refractory/unexplained (74%) and other (16%). Median (IQR) symptom and health status scores were: cough VAS 63 (41-81) mm, LCQ total 10 (8-13), EQ-5D index 0.74 (0.67-0.88) and EQ-5D VAS 66 (50-80). Mean (SD) EQ-5D index for refractory cough was 0.747 (0.221). EQ-5D index was associated with LCQ (ρ=0.30; p The systematic review identified 4 studies that reported EQ-5D-5L. Mean (SD) EQ-5D index was 0.80 (0.17) in chronic obstructive pulmonary disease (Nolan, C. M. et al. Thorax 2016; 6:493) and was 0.69 (0.22) in interstitial lung disease (Wapenaar, M. et al. Chron Respir Dis 2016; 1:1479972316674425). Conclusion: Generic health status in chronic cough is impaired and is modestly associated with LCQ but not with cough VAS. Further studies are need to assess health economics with EQ-5D and LCQ in chronic cough.

Cough is a predominant feature of respiratory infection and, in tuberculosis, is of prime importance for transmitting infection. Tuberculosis is transmitted by the air, yet the process by which bacilli are aerosolized has received little attention. Features of cough may account for differences in transmission rates from source cases of pulmonary disease. We review the literature on the mechanisms and characteristics of cough in tuberculosis in the context of the dissemination of infection. Coughing is probably more important than other respiratory maneuvers, and characteristics of mucus may have an important role but data are scarce. Direct mechanisms of cough in tuberculosis are unknown, as are temporal and other patterns that correlate with the release of viable airborne bacilli. Other than antituberculous chemotherapy and masks, there are few methods of modulating cough in tuberculosis. This is an increasingly important area for research.

Nitrofurantoin has well-described associations with a range of adverse pulmonary effects. We report the case of a 72-year old woman with relapsing pneumonitis secondary to the intermittent use of nitrofurantoin, a pattern of disease not well-represented in the literature. The case is also noteworthy as the diagnosis was initially overlooked due to the circumstances of the patient’s medication use. Lung biopsy was avoided by detailed history taking.

We call for wider measurement of clinical variables in cough in order to define phenotypes and advance cough research http://ow.ly/JXnIz

From a dissertation read before the Society on Friday, 4th November, 1966 The subject of this dissertation is Computers in Medicine and even those who have had nothing to do with these machines will be unable to ignore them in the very near future. A brief account of how they work is given here, followed by the description of a few of their applications in Medicine. In fact, learning to programme the machine is very simple, and the University Computer unit runs a special course three times a year for this purpose. Many people think of the computer as something between a glorified adding machine and a sort of god that can do anything, whereas in fact the truth lies somewhere in between.

Introduction and objectives The afferent receptor TRPV1 is implicated in the cough reflex. Several single nucleotide polymorphisms (SNPs) in TRPV1 appear to be associated with symptoms of cough in the general population. 1 We investigated whether such SNPs are associated with the objective measures of cough reflex sensitivity and 24-hour cough frequency (CF24) in chronic cough. Methods Patients were recruited from a specialist cough clinic with cough >2 months’ duration as the only or predominant symptom. Each underwent measurement of C5 (minimum concentration of capsaicin required to produce 5 coughs) and wore the Leicester Cough Monitor for 24 h. Saliva samples were taken to extract DNA and genotype six SNPs of TRPV1 : rs161365, rs17706630, rs2277675, rs222741, rs150854 and rs224498. Mean values of C5 and CF24 were compared across genotypes and univariate linear regression was used to analyse the per minor allele associations with each outcome for each SNP, on the assumption their effects would be additive. 1 Results 57 patients were recruited with underlying diagnoses including unexplained chronic cough (n = 43), asthma (n = 7) and gastro-oesophageal reflux (n = 2). 42 (74%) were female, and median (IQR) age and duration of cough was 60 (54–66) years and 5 (3–12) months, respectively. Median (IQR) C5 was 7.8 (3.9–15.6) μM/L and cough frequency 399 (181–651) coughs/24 h. Genotype frequencies were as shown (Table). There was no evidence for an association between TRPV1 polymorphisms and C5 or CF24. This was the case regardless of diagnosis. Conclusion This small study did not provide support for a large effect of TRPV1 polymorphism on cough frequency or cough reflex sensitivity in chronic cough. However, we lacked power to detect small/modest effects. Reference Smit, et al . Respir Res 2012; 13 :26.

Introduction Patterns of cough in tuberculosis influence transmission of disease yet have been little studied. We report the prevalence, duration, severity and frequency of coughing in tuberculosis. Method The first part was a retrospective review of the medical records of all individuals diagnosed with pulmonary tuberculosis (PTB) at our hospital during 2012–3. The reported presence and duration of coughing was noted. In the second part of the study, successive patients with an ultimate diagnosis of PTB wore the Leicester Cough Monitor for 24 h prior to commencing treatment. Controls had latent TB infection (LTBI). Participants rated their cough severity from 0–100 with a visual analogue scale (VAS). Cough characteristics were compared with other clinical variables. Results 108 cases of PTB from 2012–3 were included. 82 reported cough of median (IQR) duration 4 (1–8) weeks. There was a significant association of the presence of cough with TB sputum culture positivity (odds ratio, 11.0; 95% confidence interval, 2.5–50.0) but not gender, smoking, smear positivity, cavitary disease or extent of radiographic change. No clear predictor of the duration of cough was identified and there were too few patients to estimate the effect of TB strain. Cough frequency was measured in subjects with sputum smear positive PTB (S+; n = 20), smear negative PTB (S-; n = 10) and LTBI (n = 11). Variability was high: median (IQR) cough rates were 238 (121–701), 126 (15–395) and 11 (7–56) coughs/24 h, respectively, and not significantly different for S+ vs. S- (figure). For active TB, cough rates were reduced overnight (2.8 [0.2–12.4] vs. 12.7 [3.3–23.4] coughs/h for night vs. day, respectively; p = 0.01). No effect of smoking was detected, nor was there a correlation between cough frequency and radiographic extent of disease, cavities or time to sputum culture positivity. Cough severity was higher for S+ than S- but also variable and the difference not statistically significant (VAS: 60 [13–94] vs. 22 [1.5–70] respectively; p = 0.41). Severity correlated with cough frequency in active tuberculosis (Spearman’s r = 0.60, p = 0.001). Conclusion Cough in TB reduces overnight and is related to culture positivity. Bacterial burden and extent of disease may not be important. Other determinants of cough await characterisation.

Introduction and objective Cough is predominant in pulmonary tuberculosis and transmits infection, yet it is unclear how rapidly it responds to treatment. We explored changes in objectively-measured cough frequency during TB therapy with respect to other markers of disease. Method Before or on commencing anti-tuberculous treatment, consecutive patients with pulmonary tuberculosis wore the Leicester Cough Monitor for 24 h, a device comprising a small digital audio recorder and microphone with software for cough detection. Those with a baseline cough frequency greater than the upper limit of normal ( c. 100 coughs/24 h [c/24h]) were asked to undergo repeat monitoring during initial hospitalisation (if applicable), and later to coincide with routine clinic attendance or directly observed therapy (DOT). Results Median baseline cough frequency was 203 (IQR 75–470) c/24 h in all participants (n = 44), and >100 c/24 h in 32 (73%). 22 patients were willing and available to undergo serial cough monitoring (12 current smokers, 18 sputum smear positive disease [12 also with visible lung cavities], and one with HIV). Three had isoniazid-resistant disease; the remainder were fully drug-sensitive. All were eventually treated successfully. None had other respiratory diagnoses. Cough frequency in the majority declined consistently during therapy with substantial improvements by one week (Figure 1). At 2 and/or 8 weeks, five patients had a higher cough frequency than at baseline. Amongst these slow responders there was initial extensive radiographic change (n = 1), poor drug adherence with ongoing weight loss (n = 1), a paradoxical reaction to treatment with the development of a paraspinal abscess (n = 1), and, in the patient with HIV, persistent sputum smear positivity at 8 weeks with minimal radiographic improvement despite DOT and normal plasma rifampicin levels. One other patient had a highly variable cough frequency during the first 8 weeks of treatment. There was no evidence for an effect of isoniazid resistance, cavitary disease, smear status or smoking on early rates of cough resolution, although there was a trend towards relatively higher cough frequencies in smokers than non-smokers at the end of treatment ( p = 0.100). Conclusions Objective cough frequency measurement is feasible in tuberculosis and could provide a novel biomarker of treatment response.

Introduction and objective Cough is prominent in pulmonary tuberculosis (TB) and transmits infection, yet no tool has been validated for assessing cough symptoms. We evaluated the Leicester Cough Questionnaire (LCQ) for measuring cough-related quality of life (QOL) in TB. Method The face validity of the LCQ was evaluated by structured interviews with patients and a multi-disciplinary team (MDT) discussion (respiratory physicians and nurses). Consecutive patients with TB completed the LCQ just before or within 7 days of starting therapy; a subgroup completed a repeat questionnaire approximately two weeks after the first. Internal reliability (inter-relatedness between items), concurrent validity (association with cough severity visual analogue scale [VAS] score and 24-hour cough frequency measured with the Leicester Cough Monitor), and responsiveness were evaluated. Results The MDT and patients thought the LCQ to be relevant, comprehensive and useful in TB and no modifications were suggested. Forty patients completed the questionnaire before (n = 29) or just after (n = 11) the start of treatment. Internal reliability of responses was high (Cronbach’s α = 0.93). LCQ scores were correlated with both the VAS (Spearman’s ρ = -0.69 [95% confidence intervaI -0.83 to -0.46], p < 0 0.0001) and 24-hour cough frequency (ρ = -0.36 [-0.62 to -0.04], p = 0 .023), and were worse pre-treatment in culture-positive compared to culture-negative disease (median 12.4 [IQR 8.5–17.4] vs 18.7 [17.8–19.6] respectively, p = 0 .052). There was no evidence of association with other markers of disease severity (sputum smear positivity, lung cavities and radiographic extent of disease), but a trend towards worse LCQ scores amongst current smokers than non-smokers (12.6 [8.3–14.4] vs 17.1 [11.1–21.0] respectively, p = 0 .075). All patients who repeated the questionnaire appeared adherent to TB medication. There were substantial improvements in LCQ responses after a median of 14 (10–14) days’ treatment (n = 12; median [IQR] score 9.1 [8.1–14.5] at baseline, 18.3 [14.5–19.4] at two weeks, median improvement 5.1 [1.8–9.7], p = 0 .003; Figure 1). The effect size of the change in LCQ scores was 1.17. Conclusion The LCQ is a valid instrument for evaluating cough-related QOL in TB and may be a useful outcome measure to evaluate therapy.

Introduction Cough is the unique respiratory symptom. Although associated with a range of conditions it has been little studied in acute respiratory disease. We describe cough frequency and cough-related quality of life in this group. Method Participants had a diagnosis of acute exacerbation of asthma (asthma), chronic obstructive pulmonary disease (AECOPD), or lower respiratory tract infection (including community-acquired pneumonia) in the absence of the other respiratory disease (LRTI). Quality of life was measured with the Leicester Cough Questionnaire (LCQ-acute), cough severity with a visual analogue scale (VAS) and 24-hour cough frequency with the Leicester Cough Monitor. Results 40 patients were recruited within a median (interquartile range) of 1 (1–2.3) day ( ) of hospital admission. Median (IQR) age was 57 (41–71) and 63% were female. Geometric mean ± log 10­ SD cough frequencywas high: 19.7 ± 1.36, 33.8 ± 2.02 and 23.6 ± 1.31 coughs/h for asthma (n = 11), AECOPD (n = 15) and LRTI (n = 14) respectively (Figure); median (IQR) cough bouts/24h: 81 (54–210), 148 (97–197) and 129 (67–197). There was no significant difference between disease groups in these values (p > 0.05 for all two-way comparisons). Diurnal variation and median numbers of coughs/ bout were similar between groups. The 48% of patients who were current smokers coughed more than non-smokers (33.6 ± 1.91 vs 20.2 ± 1.38 coughs/h, p = 0.07). No difference in cough frequency was detected amongst the 25% taking angiotensin converting enzyme inhibitors. Gender had no significant overall effect. Median (IQR) VAS scores were 39 (32–86), 73 (53–100) and 82 (48–91) for asthma, AECOPD and LRTI respectively with no significant difference between them. Cough severity showed a significant correlation with 24-hour cough frequency overall (Spearman’ coefficient 0.33, p = 0.05). LCQ-acute scores were lower for LRTI (8.4; 6.4–9.5) than asthma (14.7; 10.7–17.5); p = 0.01 (Figure 1). Neither was significantly different from those for AECOPD (11.5; 8.5–15.6). Quality of life did not correlate with cough frequency (Spearman’ coefficient -0.13; p = 0.48). Conclusion Cough frequency in acute respiratory disease is high but with high variation. Cough frequency accounts for only part of morbidity in these conditions.

Summary Mat-supported jackup rigs often experience mat penetrations approaching the thickness of the mat in soft soil penetrations approaching the thickness of the mat in soft soil areas. Data obtained with an electronic bottom sensor show that actual mat penetrations differ from divers' observations because of a soil mound that forms near the mat's edge. The paper compares the mat penetration data with various bearing capacity procedures and strength data to help assess which procedure gives the most accurate prediction. The paper describes geologic features and soil properties that may influence the foundation performance of these rigs. The paper concludes by performance of these rigs. The paper concludes by recommending types of geophysical and geotechnical studies to be performed to evaluate the expected foundation performance of mat-supported rigs more thoroughly. performance of mat-supported rigs more thoroughly. Introduction About 60% of the offshore oil and gas exploration is being conducted with a fleet of more than 350 mobile jackup drilling rigs. Although there are many different mobile rig designs, the rigs can be divided into two broad categories according to their foundation type:individual footings ormat-supported. Many of the mats are A-shaped. Mat-supported rigs have a much larger bearing area and develop lower bearing pressures than rigs with independent footings. The lower bearing pressures enable mat-supported rigs to operate in areas covered by very soft clay soils with only a few feet of mat penetration below the seafloor. Observed mat penetrations, however, can approach the mat thickness in active delta areas around the world, such as the Mississippi River, where the soils are very soft underconsolidated clays. In these cases, an accurate measurement of the mat penetration and an assessment of the resulting foundation penetration and an assessment of the resulting foundation stability is important since designers caution against using the rigs at locations where the mat top penetrates below the seafloor. Hirst et al. showed that foundation performance of mat-supported jackup rigs was safe and performance of mat-supported jackup rigs was safe and acceptable as indicated by a record totaling 176 rig years without loss of a rig due to wind, wave, or current activities during drilling. Their performance data do, however, indicate that vertical and lateral movements have occurred in very weak soils during four severe huricanes. The purpose of this paper is to assess the geotechnical and geological factors that may influence the foundation performance of mat-supported jackup rigs operating in areas with very soft clay soils. The paper then presents a series of field measurements made at two sites in the West Delta Area to determine soil strength characteristics and mat penetration at various stages during rig placement and later, after Hurricane Allen (July 1980). These measurements show:classical bearing capacity equations underpredict actual mat penetrations of a jackup rig,a soil mound forms adjacent to the edge of the mat, resulting in divers making misleading observations of actual mat penetration below the seafloor, andthe method of placement can greatly influence mat penetration. Later sections describe the type of soil-strength data that should be used with bearing capacity equations to allow more accurate predictions of mat penetration in very soft deltaic clay predictions of mat penetration in very soft deltaic clay soils. JPT P. 2958

Abstract Even though mat-supported mobile jack-up rigs are designed to develop low seafloor bearing pressures, the observed mat penetration in soft soil areas may approach the thickness of the mat. An accurate measurement of penetration is often critical since designers caution against using the rig at locations where the top of the mat penetrates below the seafloor. Geological features and geotechnical properties of very weak soils in areas such as the Mississippi River Delta also greatly influence foundation perforJllance. This paper describes how ge010gic features and geotechnical properties can influence the foundation performance of jack-up rigs and includes field performance measurements at two sites during rig placement and later, after Hurricane Allen. The field measurements indicate the method of placement can greatly influence mat penetration. An electronic bottom sensor proved very useful inetermining the actual mat penetration since diver's observations produced misleading indications of mat penetration below the seafloor due to a mound of soil that forms near the mat edge. The observed performance data are used to develop an improved method to more accurately predict mat penetration in very soft deltaic clays than possible with classical bearing capacity theory and undisturbed shear strengths of cohesive soils. The paper concludes by recommending that integrated geotechnical and geophysical studies be performed to develop a better understanding of geologic and geotechnical factors that can influence foundation performance of a mat-supported jack-up rig. Introduction About 60 percent of the offshore oil and gas exploration is being conducted with a fleet of over 250 mobile jack-up drilling rigs. Although there are many different mobile rig designs, the rigs can be divided into two broad categories according to their foundation type:individual footings, ormat-supported. Many of the mats are A-shaped. Mat-supported rigs have a much larger bearing area and develop lower bearing pressures than rigs with independent footings. The lower bearing pressures enable mat-supported rigs to operate in areas covered by very soft clay soils with only a few feet of mat penetration below the seafloor. Observed mat penetrations, however, can approach the mat thickness in active delta areas around the world, such as the Mississippi River where the soi1s are very soft, underconso1idated c1ays. In these cases, an accurate measurement of the mat penetration and an assessment of the resulting foundation stability is important since designers caution against using the rigs at locations where the mat top penetrates below the seafloor. Hirst et al (1976) showed that foundation performance of mat-supported jack-up rigs was safe and acceptable as indicated by a record totaling 176 rig years without loss of a rig due to wind, wave, or current activities during drilling. Their performance data does, however, indicate that vertical and lateral movements have occurred in very weak soils during four severe hurricanes.