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Samantha J Thulborn,1,2 Alessandro Ceroni,3 Koirobi Haldar,4 Vijay Mistry,4 Jennifer L Cane,1,2 Christopher E Brightling,4,5 Michael R Barer,4 Mona Bafadhel1 1Respiratory Medicine Unit, Nuffield Department of Medicine, University of Oxford, Oxford, UK; 2Oxford NIHR Biomedical Research Centre, University of Oxford, Oxford, UK; 3Target Discovery Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK; 4Department of Immunity, Infection and Inflammation, University of Leicester, Leicester, UK; 5Institute for Lung Health, University of Leicester, Leicester, UKCorrespondence: Mona BafadhelRespiratory Medicine Unit, NDM Research Building, Old Campus Road, University of Oxford, Oxford OX3 7FZ, UKTel +44 1865 612898Email mona.bafadhel@ndm.ox.ac.ukBackground: Non-typeable Haemophilus influenzae (NTHi) is the most commonly found pathogen in the lower respiratory airways of patients with COPD. NTHi is predominantly regarded as an intracellular pathogen; however, like most pathogens, it can exist and co-exist in two broad forms: cell-associated (intracellularly or adhered to cells) or cell-dissociated (biofilm dispersed or planktonic). We sought to investigate if cell-dissociated NTHi can be detected from the sputum of COPD patients and assess this relationship to disease severity and airway inflammation.Methods: DNA was extracted from the sputum plug and cell-free supernatant to quantify absolute (cell-associated and cell-dissociated NTHi) and cell-dissociated NTHi, respectively, from 87 COPD subjects attending an observational longitudinal COPD exacerbation study. NTHi was quantified using TaqMan hydrolysis probes, targeting the OMP P6 gene using qPCR.Results: At stable state cell-dissociated NTHi was detected 56% of subjects with a median (IQR) of 9.95x102 gene copies (1.26x102 to 1.90x104). Cell-dissociated NTHi correlated with absolute NTHi levels (r=0.34, p< 0.01) but not airway inflammation or spirometry at stable state. At exacerbation, cell-dissociated NTHi correlated with lung function (FEV1 r=0.629, p=0.005; FEV1%predicted r=0.564, p=0.015; FVC r=0.476 p=0.046) and sputum neutrophilic inflammation (% neutrophils r=0.688, p=0.002; total neutrophils r=0.518, p=0.028).Conclusion: In patients with COPD, NTHi can exist in both cell-associated and cell-dissociated forms. Cell-dissociated NTHi is associated with neutrophilic airway inflammation during exacerbations of COPD and may be a driving factor in worsening lung function during these episodes.Keywords: NTHi, infection, neutrophils, COPD

BackgroundReliably identifying patients at increased risk for coronavirus disease (COVID-19) complications could guide clinical decisions, public health policies, and preparedness efforts. Multiple studies have attempted to characterize at-risk patients, using various data sources and methodologies. Most of these studies, however, explored condition-specific patient cohorts (eg, hospitalized patients) or had limited access to patients’ medical history, thus, investigating related questions and, potentially, obtaining biased results. ObjectiveThis study aimed to identify factors associated with COVID-19 complications from the complete medical records of a nationally representative cohort of patients, with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. MethodsWe studied a cohort of all SARS-CoV-2–positive individuals, confirmed by polymerase chain reaction testing of either nasopharyngeal or saliva samples, in a nationwide health organization (covering 2.3 million individuals) and identified those who suffered from serious complications (ie, experienced moderate or severe symptoms of COVID-19, admitted to the intensive care unit, or died). We then compared the prevalence of pre-existing conditions, extracted from electronic health records, between complicated and noncomplicated COVID-19 patient cohorts to identify the conditions that significantly increase the risk of disease complications, in various age and sex strata. ResultsOf the 4353 SARS-CoV-2–positive individuals, 173 (4%) patients suffered from COVID-19 complications (all age ≥18 years). Our analysis suggests that cardiovascular and kidney diseases, obesity, and hypertension are significant risk factors for COVID-19 complications. It also indicates that depression (eg, males ≥65 years: odds ratio [OR] 2.94, 95% CI 1.55-5.58; P=.01) as well as cognitive and neurological disorders (eg, individuals ≥65 years old: OR 2.65, 95% CI 1.69-4.17; P

Leena M George,1,* Richard D Haigh,1,* Vijay Mistry,1 Koirobi Haldar,1 Michael R Barer,1 Marco R Oggioni,2 Christopher E Brightling1 1Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, UK; 2Department of Genetics, University of Leicester, Leicester, UK *These authors contributed equally to this work Purpose: Moraxella catarrhalis is implicated in the pathogenesis of some COPD exacerbations. We sought to investigate whether the M. catarrhalis strain is variable between COPD subjects; that an exacerbation is associated with acquisition of a new strain and that certain strains are more commonly associated with exacerbations. Patients and methods: Sputum samples were collected at stable and exacerbation visits from COPD subjects from a single center as part of the COPDMAP consortium. Samples identified as M. catarrhalis positive by qPCR were recultured in liquid cultures grown to extract genomic DNA; underwent Illumina MiSeq and bacterial genome sequences were de novo assembled and Multi Locus Sequence Type (MLST) was determined. Results: Thirty-five samples were obtained from 18 subjects. These included 13 stable and 22 exacerbation samples. The diversity between samples was very large with 25 different M. catarrhalis MLSTs being identified out of the 35 samples of which 12 MSLTs have not been described previously. Change and persistence of M. catarrhalis strain were observed between stable visits, from stable to exacerbation and vice-a-versa, and between exacerbation visits. Conclusion: Sputum M. catarrhalis strains exhibit marked diversity within and between COPD subjects. Acquisition of a new strain is common between stable and exacerbation events such that no strain is specifically associated with an exacerbation. Keywords: COPD, Moraxella catarrhalis, strain change, exacerbation

Samantha J Thulborn,1 Madiha Dilpazir,2 Koirobi Haldar,3 Vijay Mistry,3 Christopher E Brightling,3 Michael R Barer,3 Mona Bafadhel1 1Respiratory Medicine Unit, Nuffield Department of Medicine, University of Oxford, 2Department of Biological and Medical Sciences, Oxford Brookes University, Oxford, 3Department of Immunity, Infection & Inflammation, University of Leicester, Leicester, UK Background: Pentraxin 3 (PTX3) is an acute phase protein, involved in antibacterial resistance. Recent studies have shown PTX3 levels to be elevated in the presence of a bacterial infection and in a murine sepsis model.Objective: We aim to investigate if sputum PTX3 can be used as a biomarker for bacterial infection in subjects with COPD.Materials and methods: Sputum samples from 142 COPD patients (102 men) with a mean (range) age of 69 years (45–85) and mean (SD) post-bronchodilator percentage predicted forced expiratory volume in 1 second (FEV1) of 50% (19) were analyzed for PTX3, using a commercial assay at stable state and during an exacerbation. Association with bacteria, from culture, quantitative real-time polymerase chain reaction (qPCR) and colony-forming units (CFU) was investigated.Results: The geometric mean (95% CI) PTX3 level at stable state was 50.5 ng/mL (41.4–61.7). PTX3 levels correlated with absolute neutrophil count in sputum (r=0.37; P105 CFU/mL at stable state) with a receiver-operating characteristic (ROC) area under the curve (AUC) of 0.59 and 95% confidence interval (CI) 0.43–0.76 (P=0.21). During an exacerbation, there was a modest increase in PTX3 (fold difference 0.15, 95% of difference 0.02–0.29; P=0.02), and PTX3 fared better at identifying a bacteria-associated exacerbation (ROC AUC 0.65, 95% CI 0.52–0.78, P=0.03).Conclusion: PTX3 is associated with bacterial infection in patients with COPD, but its utility as a biomarker for identifying a bacteria-associated exacerbation warrants further studies. Keywords: TNF-inducible gene 14 protein, infection, sputum

Mona Bafadhel,1 Koirobi Haldar,2 Bethan Barker,2,3 Hemu Patel,4 Vijay Mistry,2,3 Michael R Barer,2–4 Ian D Pavord,1 Christopher E Brightling2,3 1Respiratory Medicine Unit, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK; 2Department of Infection, Immunity and Inflammation, University of Leicester, 3Institute for Lung Health, National Institute for Health Research Respiratory Biomedical Research Unit, Glenfield Hospital, University of Leicester, 4Department of Clinical Microbiology, University Hospitals of Leicester NHS Trust, Leicester, UK Background: Potentially pathogenic microorganisms can be detected by quantitative real-time polymerase chain reaction (qPCR) in sputum from patients with COPD, although how this technique relates to culture and clinical measures of disease is unclear. We used cross-sectional and longitudinal data to test the hypotheses that qPCR is a more sensitive measure of bacterial presence and is associated with neutrophilic airway inflammation and adverse clinical outcomes.Methods: Sputum was collected from 174 stable COPD subjects longitudinally over 12 months. Microbial sampling using culture and qPCR was performed. Spirometry and sputum measures of airway inflammation were assessed.Findings: Sputum was qPCR-positive (>106 copies/mL) in 77/152 samples (Haemophilus influenzae [n=52], Moraxella catarrhalis [n=24], Streptococcus pneumoniae [n=19], and Staphylococcus aureus [n=7]). Sputum was culture-positive in 50/174 samples, with 49 out of 50 culture-positive samples having pathogen-specific qPCR bacterial loads >106 copies/mL. Samples that had qPCR copy numbers >106/mL, whether culture-positive or not, had increased sputum neutrophil counts. H. influenzae qPCR copy numbers correlated with sputum neutrophil counts (r=0.37, P106/mL three or more times in 19 patients, eight of whom were repeatedly sputum culture-positive. Persistence, whether defined by culture, qPCR, or both, was associated with a higher sputum neutrophil count, lower forced expiratory volume in 1 second (FEV1), and worsened quality of life.Interpretation: qPCR identifies a significant number of patients with potentially bacteria-associated neutrophilic airway inflammation and disease that are not identified by traditional culture-based methods. Keywords: H. influenzae, qPCR, sputum

Bethan L Barker,1 Susan McKenna,1 Vijay Mistry,1 Mitesh Pancholi,1 Hemu Patel,2 Koirobi Haldar,3 Michael R Barer,3 Ian D Pavord,4 Michael C Steiner,1 Christopher E Brightling,1 Mona Bafadhel4 1Institute for Lung Health, NIHR Respiratory Biomedical Research Unit, Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, United Kingdom; 2Department of Clinical Microbiology, University Hospitals of Leicester NHS Trust, Leicester, United Kingdom; 3Department of Infection, Immunity, and Inflammation, University of Leicester, Leicester, United Kingdom; 4Respiratory Medicine Unit, Nuffield Department of Clinical Medicine, University of Oxford, Old Road Campus, Oxford, United Kingdom Background: Nutritional depletion is an important manifestation of chronic obstructive pulmonary disease (COPD), which has been related to systemic inflammation. It remains unclear to what degree airway inflammation contributes to the presence or progression of nutritional depletion. Objectives: To determine whether airway inflammation and lung bacterial colonization are related to nutritional status or predict progressive weight loss and muscle atrophy in patients with COPD. Methods: Body composition using dual energy X-ray absorptiometry, indices of airway inflammation, and bacterial colonization were measured in 234 COPD patients. Systemic inflammation was assessed from serum C reactive protein (CRP) and circulating total and differential leukocyte counts. Nutritional depletion was defined as a body mass index (BMI) less than 21 kg/m2 and/or fat-free mass index (FFMI) less than 15 or 17 kg/m2 in women and men, respectively. FFMI was calculated as the fat-free mass (FFM) corrected for body surface area. Measurements were repeated in 94 patients after a median 16-month follow-up. Regression analysis was used to assess the relationships of weight change and FFM change with indices of bacterial colonization and airway and systemic inflammation. Results: Nutritional depletion occurred in 37% of patients. Lung function was worsened in patients with nutritional depletion compared to those without (forced expiratory volume in 1 second 1.17 L versus 1.41 L, mean difference 0.24, 95% confidence interval 0.10 to 0.38, P

Abstract Background Laboratory testing is one of the fastest growing areas of health services spending in Canada. We examine the extent to which increases in laboratory expenditures might be explained by testing that is consistent with guidelines for the management of chronic conditions, by analyzing fee-for-service physician payment data in British Columbia from 1996/97 and 2005/06. Method We used direct standardization to quantify the effect on laboratory expenditures from changes in: fee levels; population growth; population aging; treatment prevalence; expenditure on recommended tests for those conditions; and expenditure on other tests. The chronic conditions selected were those with guidelines containing laboratory recommendations developed by the BC Guidelines and Protocol Advisory Committee: diabetes, hypertension, congestive heart failure, renal failure, liver disease, rheumatoid arthritis, osteoarthritis and dementia. Result Laboratory service expenditures increased by $98 million in 2005/06 compared to 1996/97, or 3.6% per year after controlling for population growth and aging. Testing consistent with guideline-recommended care for chronic conditions explained one-third (1.2% per year) of this growth. Changes in treatment prevalence were just as important, contributing 1.5% per year. Hypertension was the most common condition, but renal failure and dementia showed the largest changes in prevalence over time. Changes in other laboratory expenditure including for those without chronic conditions accounted for the remaining 0.9% growth per year. Conclusion Increases in treatment prevalence were the largest driver of laboratory cost increases between 1996/97 and 2005/06. There are several possible contributors to increasing treatment prevalence, all of which can be expected to continue to put pressure on health care expenditures.

Abstract Background Up to 42% of all stroke patients do not get out of the house as much as they would like. This can impede a person’s quality of life. This study is testing the clinical effectiveness and cost effectiveness of a new outdoor mobility rehabilitation intervention by comparing it to usual care. Methods/design This is a multi-centre parallel group individually randomised, controlled trial. At least 506 participants will be recruited through 15 primary and secondary care settings and will be eligible if they are over 18 years of age, have had a stroke and wish to get out of the house more often. Participants are being randomly allocated to either the intervention group or the control group. Intervention group participants receive up to 12 rehabilitation outdoor mobility sessions over up to four months. The main component of the intervention is repeated practice of outdoor mobility with a therapist. Control group participants are receiving the usual intervention for outdoor mobility limitations: verbal advice and provision of leaflets provided over one session. Outcome measures are being collected using postal questionnaires, travel calendars and by independent assessors. The primary outcome measure is the Social Function domain of the SF36v2 quality of life assessment six months after recruitment. The secondary outcome measures include: functional ability, mobility, the number of journeys (monthly travel diaries), satisfaction with outdoor mobility, mood, health-related quality of life, resource use of health and social care. Carer mood information is also being collected. The mean Social Function score of the SF-36v2 will be compared between treatment arms using a multiple membership form of mixed effects multiple regression analysis adjusting for centre (as a fixed effect), age and baseline Social Function score as covariates and therapist as a multiple membership random effect. Regression coefficients and 95% confidence intervals will be presented. Discussion This study protocol describes a pragmatic randomised controlled trial that will hopefully provide robust evidence of the benefit of outdoor mobility interventions after stroke for clinicians working in the community. The results will be available towards the end of 2012. Trial registration ISRCTN58683841

Abstract Background Accounting for 36% of public spending on health care in Canada, hospitals are a major target for cost reductions through various efficiency initiatives. Some provinces are considering payment reform as a vehicle to achieve this goal. With few exceptions, Canadian provinces have generally relied on global and line-item budgets to contain hospital costs. There is growing interest amongst policy-makers for using activity based funding (ABF) as means of creating financial incentives for hospitals to increase the 'volume' of care, reduce cost, discourage unnecessary activity, and encourage competition. British Columbia (B.C.) is the first province in Canada to implement ABF for partial reimbursement of acute hospitalization. To date, there have been no formal examinations of the effects of ABF policies in Canada. This study proposal addresses two research questions designed to determine whether ABF policies affect health system costs, access and hospital quality. The first question examines the impact of the hospital funding policy change on internal hospital activity based on expenditures and quality. The second question examines the impact of the change on non-hospital care, including readmission rates, amount of home care provided, and physician expenditures. Methods/Design A longitudinal study design will be used, incorporating comprehensive population-based datasets of all B.C. residents; hospital, continuing care and physician services datasets will also be used. Data will be linked across sources using anonymized linking variables. Analytic datasets will be created for the period between 2005/2006 and 2012/2013. Discussion With Canadian hospitals unaccustomed to detailed scrutiny of what services are provided, to whom, and with what results, the move toward ABF is significant. This proposed study will provide evidence on the impacts of ABF, including changes in the type, volume, cost, and quality of services provided. Policy- and decision-makers in B.C. and elsewhere in Canada will be able to use this evidence as a basis for policy adaptations and modifications. The significance of this proposed study derives from the fact that the change in hospital funding policy has the potential to affect health system costs, residents' access to care and care quality.

Abstract Background Although Haemophilus influenzae type b (Hib), Staphylococcus aureus and Moraxella catarrhalis are important causes of invasive and mucosal bacterial disease among children, co-carriage with Streptococcus pneumoniae during infancy has not been determined in West Africa. Methods Species specific PCR was applied to detect each microbe using purified genomic DNA from 498 nasopharyngeal (NP) swabs collected from 30 Gambian neonates every two weeks from 0 to 6 months and bi-monthly up to 12 months. Results All infants carried S. pneumoniae, H. influenzae and M. catarrhalis at several time points during infancy. S.pneumoniae co-colonized the infant nasopharynx with at least one other pathogen nine out of ten times. There was early colonization of the newborns and neonates, the average times to first detection were 5, 7, 3 and 14 weeks for S. pneumoniae, H. influenzae, M. catarrhalis and S. aureus respectively. The prevalence of S. pneumoniae, H. influenzae and M. catarrhalis increased among the neonates and exceeded 80% by 13, 15 and 23 weeks respectively. In contrast, the prevalence of S. aureus decreased from 50% among the newborns to 20% amongst nine-week old neonates. S. pneumoniae appeared to have a strong positive association with H. influenzae (OR 5.03; 95% CI 3.02, 8.39; p < 0.01) and M. catarrhalis (OR 2.20; 95% CI 1.29; p < 0.01) but it was negatively associated with S. aureus (OR 0.53; 95% CI 0.30, 0.94; p = 0.03). Conclusion This study shows early acquisition and high co-carriage of three important respiratory pathogens with S. pneumoniae in the nasopharyngeal mucosa among Gambian neonates and infants. This has important potential implications for the aetiology of respiratory polymicrobial infections, biofilm formation and vaccine strategies.

Abstract Background Though vascular factors may be important in the aetiology of late-life depression, it is not clear whether they have a major effect on the risk of depression after a stroke. We investigated the relationship between physiological, biochemical, neuro-imaging and socio-economic factors and late-phase post-stroke depression in a cross-sectional case-control study. Methods People living at home at least 9 months after a stroke were interviewed using a structured proforma. Depression was diagnosed according to DSM-IV criteria, together with a Montgomery Asberg (MADRS) score >17. Stroke survivors of similar age and functional status but without symptoms of, or recent treatment for, depression and with MADRS score Results Stroke survivors with depression were more likely than controls to have been smokers, to have had hypertension or peripheral arterial disease, and to have had more than one stroke or multiple discrete brainscan lesions. In univariate analysis they had significantly higher blood pressure, lower Mini-Mental State (MMSE) scores, higher serum homocysteine and lower folate levels, as well as more extensive white matter and basal ganglia changes on brainscan. In logistic regression, previous hypertension (OR 3.4), peripheral vascular disease (OR 4.7), number of strokes (OR 2), MMSE score (OR 0.76) and basal ganglia changes (OR 2.2), were independently associated with depression. Conclusion These results suggest that patients with hypertension, hyperhomocysteinaemia and other factors associated with cerebral small vessel disease, may be more susceptible to post-stroke depression. Future intervention trials should focus on such high risk groups.

Abstract Background Few measures of health related quality of life exist for use with preschool aged children. The objective of this study was to assess reliability and validity of a new multidimensional generic measure of health-related quality of life developed for use with preschool children. Methods Cross-sectional survey sent to parents as their child turned 3 1/2 years of age. The setting was the province of British Columbia, Canada. Patients included all babies admitted to tertiary level neonatal intensive care units (NICU) at birth over a 16-month period, and a consecutive sample of healthy babies. The main outcome measure was a new full-length questionnaire consisting of 3 global items and 10 multi-item scales constructed to measure the physical and emotional well-being of toddlers and their families. Results The response rate was 67.9%. 91% (NICU) and 84% (healthy baby) of items correlated with their own domain above the recommended standard (0.40). 97% (NICU) and 87% (healthy baby) of items correlated more highly (≥ 2 S.E.) with their hypothesized scale than with other scales. Cronbach's alpha coefficients varied between .80 and .96. Intra-class correlation coefficients were above .70. Correlations between scales in the new measure and other instruments were moderate to large, and were stronger than between non-related domains. Statistically significant differences in scale scores were observed between the NICU and healthy baby samples, as well as between those diagnosed with a health problem requiring medical attention in the past year versus those with no health problems. Conclusions Preliminary results indicate the new measure demonstrates acceptable reliability and construct validity in a sample of children requiring NICU care and a sample of healthy children. However, further development work is warranted.

Background Recently, face mask sampling (FMS) confirmed detection of Mycobacterium tuberculosis DNA from exhaled breath in adults with tuberculosis. To date, no study has evaluated the use of FMS to detect pulmonary tuberculosis in children. We developed a method for FMS of M. tuberculosis- specific DNA in children and performed a clinical exploration to assess feasibility in children. Methods Face masks were spiked, analyzed on GeneXpert-Ultra, quantitative polymerase chain reaction, and targeted next-generation sequencing. Children with pulmonary tuberculosis were asked to wear 3 modified FFP2 masks for 30 minutes as part of an exploratory clinical study. Results Experiments with H37Ra M. tuberculosis strain showed a limit of 95% detection of 3.75 colony-forming units (95% confidence interval, 4.85–3.11) on GeneXpert-Ultra. Ten children with pulmonary tuberculosis participated in the clinical study. M. tuberculosis -specific DNA was detected on none of the face masks. Conclusions Pediatric FMS has a low limit of detection for M. tuberculosis -specific DNA in vitro. However, M. tuberculosis DNA was not detected in any of 30 masks worn by children with pulmonary tuberculosis. This suggests that FMS in this form may not be more effective for detecting M. tuberculosis in children with tuberculosis than existing methods. [ABSTRACT FROM AUTHOR]

Introduction: Tuberculosis (TB) is the leading cause of death worldwide from a single infectious agent. Bacillus Calmette-Guérin (BCG), the only licensed vaccine, provides limited protection. Controlled human infection models (CHIMs) are useful in accelerating vaccine development for pathogens with no correlates of protection; however, the need for prolonged treatment makes Mycobacterium tuberculosis an unethical challenge agent. Aerosolised BCG provides a potential safe surrogate of infection. A CHIM in BCG-vaccinated as well as BCG-naïve individuals would allow identification of novel BCG-booster vaccine candidates and facilitate CHIM studies in populations with high TB endemicity. The purpose of this study was to evaluate the safety and utility of an aerosol BCG CHIM in historically BCG-vaccinated volunteers. Methods: There were 12 healthy, historically BCG-vaccinated UK adults sequentially enrolled into dose-escalating groups. The first three received 1 × 104 CFU aerosol BCG Danish 1331 via a nebuliser. After safety review, subsequent groups received doses of 1 × 105 CFU, 1 × 106 CFU, or 1 × 107 CFU. Safety was monitored through self-reported adverse events (AEs), laboratory tests, and lung function testing. Immunology blood samples were taken pre-infection and at multiple timepoints post-infection. A bronchoalveolar lavage (BAL) taken 14 days post-infection was analysed for presence of live BCG. Results: No serious AEs occurred during the study. Solicited systemic and respiratory AEs were frequent in all groups, but generally short-lived and mild in severity. There was a trend for more reported AEs in the highest-dose group. No live BCG was detected in BAL from any volunteers. Aerosol BCG induced potent systemic cellular immune responses in the highest-dose group 7 days post-infection. Discussion: Aerosol BCG infection up to a dose of 1 × 107 CFU was well-tolerated in historically BCG-vaccinated healthy, UK adults. No live BCG was detected in the BAL fluid 14 days post-infection despite potent systemic responses, suggesting early clearance. Further work is needed to expand the number of volunteers receiving BCG via the aerosol route to refine and establish utility of this aerosol BCG CHIM. Clinical trial registration: https://clinicaltrials.gov/ , identifier NCT04777721. [ABSTRACT FROM AUTHOR]

Background and objective: Chronic cough (CC) is a prevalent yet underexplored medical condition, with limited real-world data regarding its healthcare burden. This study investigates the epidemiology, associated comorbidities, and healthcare service utilization among patients with CC. Methods: In this retrospective cohort study, adult patients with at least 3 physician diagnoses of cough over a period spanning a minimum of 8 weeks and a maximum of 12 months anytime between 2009 and 2018, were defined as patients with CC (PwCC). The reference group were adults without cough matched in a 1:1 ratio for age, sex, and place of residence. Results: The study included 91,757 PwCC, reflecting a prevalence of 5.5%. Of those, 59,296 patients (mean [SD] age, 53.9 [16.8] years; 59.6% females) were first diagnosed with CC during the study period, representing a 10-year incidence rate of 3.26% (95%CI: 3.24–3.29%). Diseases associated with the highest OR for CC included lung cancer (OR = 3.32; 95%CI: 2.90–4.25), whooping cough (OR = 3.04; 95%CI: 2.70–3.60), and respiratory infections (OR = 2.81; 95%CI: 2.74–2.88). Furthermore, PwCC demonstrated increased healthcare service utilization, leading to a higher adjusted annual estimated mean cost (USD 4038 vs. USD 1833, p < 0.001). Conclusions: Chronic cough emerges as a relatively prevalent complaint within community care, exerting a considerable economic burden. This study underscores the need for heightened awareness, comprehensive management strategies, and resource allocation to address the multifaceted challenges associated with chronic cough. [ABSTRACT FROM AUTHOR]