Imperial College London

ProfessorPaulCullinan

Faculty of MedicineNational Heart & Lung Institute

Prof of Occ and Env Respiratory Disease
 
 
 
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Contact

 

+44 (0)20 7594 7990p.cullinan

 
 
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Assistant

 

Miss Magda Wheatley +44 (0)20 7594 7990

 
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Location

 

G47Emmanuel Kaye BuildingRoyal Brompton Campus

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Summary

 

Publications

Publication Type
Year
to

331 results found

Yang Z, Lin Y, Wang S, Liu X, Cullinan P, Chung KF, Zhang Jet al., 2021, Urinary Amino-Polycyclic Aromatic Hydrocarbons in Urban Residents: Finding a Biomarker for Residential Exposure to Diesel Traffic, ENVIRONMENTAL SCIENCE & TECHNOLOGY, Vol: 55, Pages: 10569-10577, ISSN: 0013-936X

Journal article

Archangelidi O, Cullinan P, Simmonds NJ, Mentzakis E, Peckham D, Bilton D, Carr SBet al., 2021, Incidence and risk factors of cancer in individuals with cystic fibrosis in the UK; a case-control study., Journal of Cystic Fibrosis, ISSN: 1569-1993

To assess cancer incidence in the UK cystic fibrosis (CF) population and determine the associated risk factors, we undertook a nested case-control study of patients with CF, registered with the UK CF Registry. Each case with a first reported cancer between 1999 and 2017 was matched with up to 4 controls: by age (±2-years) and year of cancer diagnosis. Conditional logistic regressions were adjusted for sex, lung function (FEV1%), CF related diabetes (CFRD), F508del status, transplant status, DIOS, gastro-oesophageal reflux disease, meconium ileus, Pseudomonas aeruginosa infection, pancreatic insufficiency, proton pump inhibitor (PPI) use, IV antibiotic days and BMI. Results: From 12,886 registered patients, 146 (1.1%) cases of malignancy were identified with 14.3% of cases occurring post solid organ transplant. Site of primary cancer was available for 98 patients: 22% were gastro-intestinal in origin (77% lower, 23% upper GI), 13% skin, 13% breast and 11% lymphomas/leukaemia. In univariable analysis, transplantation increased the odds of reporting any cancer by 2.46 times (95%CI: 1.3-4.6). CFRD also increased the odds of reporting any cancer (OR 2.35; CI: 1.37-4.0) and PPI use (OR 2.0; CI 1.28-3.19). In the multivariable models significant associations with CFRD and transplant remained, while PA infection, PPI use and being overweight showed increased, but statistically insignificant risks. The incidence of GI cancer was strongly associated with CFRD (OR=4.04; 1.47-11.1). Conclusions: We observed a high incidence of lower GI cancers in our cohort which was significantly affected by the presence of CFRD. Screening for gastrointestinal cancers could benefit patients at higher risk.

Journal article

Bloom CI, Drake TM, Docherty AB, Lipworth BJ, Johnston SL, Nguyen-Van-Tam JS, Carson G, Dunning J, Harrison EM, Baillie JK, Semple MG, Cullinan P, Openshaw PJM, Alex B, Bach B, Barclay WS, Bogaert D, Chand M, Cooke GS, Filipe AD, Fletcher T, Green CA, Harrison EM, Hiscox JA, Ho AY, Horby PW, Ijaz S, Khoo S, Klenerman P, Law A, Lim WS, Mentzer AJ, Merson L, Meynert AM, Noursadeghi M, Moore SC, Palmarini M, Paxton WA, Pollakis G, Price N, Rambaut A, Robertson DL, Russell CD, Sancho-Shimizu V, Scott JT, Silva TD, Sigfrid L, Solomon T, Sriskandan S, Stuart D, Summers C, Tedder RS, Thomson EC, Thompson AAR, Thwaites RS, Turtle LCW, Zambon M, Hardwick H, Donohue C, Lyons R, Griffiths F, Oosthuyzen W, Norman L, Pius R, Fairfield CJ, Knight SR, Mclean KA, Murphy D, Shaw CA, Dalton J, Girvan M, Saviciute E, Roberts S, Harrison J, Marsh L, Connor M, Halpin S, Jackson C, Gamble C, Leeming G, Law A, Wham M, Clohisey S, Hendry R, Scott-Brown J, Greenhalf W, Shaw V, McDonald S, Keating S, Ahmed KA, Armstrong JA, Ashworth M, Asiimwe IG, Bakshi S, Barlow SL, Booth L, Brennan B, Bullock K, Catterall BWA, Clark JJ, Clarke EA, Cole S, Cooper L, Cox H, Davis C, Dincarslan O, Dunn C, Dyer P, Elliott A, Evans A, Finch L, Fisher LWS, Foster T, Garcia-Dorival I, Greenhalf W, Gunning P, Hartley C, Jensen RL, Jones CB, Jones TR, Khandaker S, King K, Kiy RT, Koukorava C, Lake A, Lant S, Latawiec D, Lavelle-Langham L, Lefteri D, Lett L, Livoti LA, Mancini M, McDonald S, McEvoy L, McLauchlan J, Metelmann S, Miah NS, Middleton J, Mitchell J, Moore SC, Murphy EG, Penrice-Randal R, Pilgrim J, Prince T, Reynolds W, Ridley PM, Sales D, Shaw VE, Shears RK, Small B, Subramaniam KS, Szemiel A, Taggart A, Tanianis-Hughes J, Thomas J, Trochu E, Tonder LV, Wilcock E, Zhang JE, Flaherty L, Maziere N, Cass E, Carracedo AD, Carlucci N, Holmes A, Massey H, Adeniji K, Agranoff D, Agwuh K, Ail D, Alegria A, Angus B, Ashish A, Atkinson D, Bari S, Barlow G, Barnass S, Barrett N, Bassford C, Baxter D, Beadsworth Met al., 2021, Risk of adverse outcomes in patients with underlying respiratory conditions admitted to hospital with COVID-19: a national, multicentre prospective cohort study using the ISARIC WHO Clinical Characterisation Protocol UK, The Lancet Respiratory Medicine, Vol: 9, Pages: 699-711, ISSN: 2213-2600

BackgroundStudies of patients admitted to hospital with COVID-19 have found varying mortality outcomes associated with underlying respiratory conditions and inhaled corticosteroid use. Using data from a national, multicentre, prospective cohort, we aimed to characterise people with COVID-19 admitted to hospital with underlying respiratory disease, assess the level of care received, measure in-hospital mortality, and examine the effect of inhaled corticosteroid use.MethodsWe analysed data from the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) WHO Clinical Characterisation Protocol UK (CCP-UK) study. All patients admitted to hospital with COVID-19 across England, Scotland, and Wales between Jan 17 and Aug 3, 2020, were eligible for inclusion in this analysis. Patients with asthma, chronic pulmonary disease, or both, were identified and stratified by age (<16 years, 16–49 years, and ≥50 years). In-hospital mortality was measured by use of multilevel Cox proportional hazards, adjusting for demographics, comorbidities, and medications (inhaled corticosteroids, short-acting β-agonists [SABAs], and long-acting β-agonists [LABAs]). Patients with asthma who were taking an inhaled corticosteroid plus LABA plus another maintenance asthma medication were considered to have severe asthma.Findings75 463 patients from 258 participating health-care facilities were included in this analysis: 860 patients younger than 16 years (74 [8·6%] with asthma), 8950 patients aged 16–49 years (1867 [20·9%] with asthma), and 65 653 patients aged 50 years and older (5918 [9·0%] with asthma, 10 266 [15·6%] with chronic pulmonary disease, and 2071 [3·2%] with both asthma and chronic pulmonary disease). Patients with asthma were significantly more likely than those without asthma to receive critical care (patients aged 16–49 years: adjusted odds ratio [OR] 1·20 [95% CI

Journal article

Ratanachina J, Amaral A, De Matteis S, Cullinan P, Burney Pet al., 2021, Farming, pesticide exposure and respiratory health: a cross-sectional study in Thailand, Occupational and Environmental Medicine, ISSN: 1351-0711

Objective: To assess the association of lung function and respiratory symptoms with farming, particularly pesticide use, in an agricultural province in Thailand.Methods: We undertook a cross-sectional survey of adults aged 40–65 in Nan province, Thailand, between May and August 2019. We randomly recruited 345 villagers and enriched the sample with 82 government employees. All participants performed post-bronchodilator spirometry and completed a questionnaire covering information on respiratory symptoms, farming activities, pesticide use and known risk factors for respiratory disease. Associations of respiratory outcomes with farming and pesticide exposures were examined by multivariable regression analysis.Results: The response rate was 94%. The prevalence of chronic airflow obstruction among villagers was 5.5%. Villagers had, on average, a lower percent predicted post-bronchodilator forced expiratory volume in one second/forced vital capacity (FEV1/FVC) than government employees (98.3% vs 100.3%; p=0.04). There was no evidence of association of lung function with farming activities, the use of specific herbicides (glyphosate and paraquat), insecticides (organophosphates and pyrethroids) or fungicides. The exceptions were poultry farming, associated with chronic cough and an increase of FEV1/FVC, and atrazine, for which duration (p-trend <0.01), intensity (p-trend <0.01) and cumulative hours (p-trend=0.01) of use were all associated with higher FEV1/FVC in an exposure–response manner. Cumulative hours (−280 mL/hour), low duration (−270 mL/year) and intensity (−270 mL/hour/year) of atrazine use were associated with lower FVC.Conclusions: Chronic airflow obstruction is uncommon among villagers of an agricultural province in Nan, Thailand. Farming and pesticide use are unlikely to be major causes of respiratory problems there.

Journal article

van der Plaat D, Edge R, Coggon D, van Tongeren M, Muiry R, Parsons V, Cullinan P, Madan Iet al., 2021, Impact of COVID-19 pandemic on sickness absence for mental ill health in National Health Service staff, Publisher: Cold Spring Harbor Laboratory

Abstract Objective: To explore the patterns of sickness absence in National Health Service (NHS) staff attributable to mental ill health during the first wave of the Covid19 epidemic in March to July 2020 Design: Case-referent analysis of a secondary data set Setting: NHS Trusts in England Participants: Pseudonymised data on 959,356 employees who were continuously employed by NHS trusts during 1 January 2019 to 31 July 2020 Main Outcome Measures: Trends in the burden of sickness absence due to mental ill health from 2019 to 2020 according to demographic, regional and occupational characteristics. Results: Over the study period, 164,202 new sickness absence episodes for mental ill health were recorded in 12.5% (119,525) of the study sample. There was a spike of sickness absence for mental ill health in March-April 2020 (899,730 days lost) compared with 519,807 days in March and April 2019; the surge was driven by an increase in new episodes of long-term absence and had diminished by May and June 2020. The increase was greatest in those aged >60 years (227%) and among employees of Asian and Black ethnic origin (109%-136%). Among doctors and dentists the number of days absent declined by 12.7%. The biggest increase was in London (122%) and the smallest in the East Midlands (43.7%); the variation between regions reflected the rates of Covid19 sickness absence during the same period. Conclusion: Although the Covid19 epidemic led to an increase in sickness absence attributed to mental ill health in NHS staff, this had substantially declined by May and June 2020, corresponding with the decrease in pressures at work as the first wave of the epidemic subsided.

Working paper

Walsh JA, Barker RE, Kon SSC, Jones SE, Banya W, Nolan CM, Patel S, Polgar O, Haselden BM, Polkey MI, Cullinan P, Man WD-Cet al., 2021, Gait speed and adverse outcomes following hospitalised exacerbation of COPD, European Respiratory Journal, ISSN: 0903-1936

Four-metre gait speed (4MGS) is a simple physical performance measure and surrogate marker of frailty that is associated with adverse outcomes in older adults. We aimed to assess the ability of 4MGS to predict prognosis in patients hospitalised with acute exacerbations of COPD (AECOPD).213 participants hospitalised with AECOPD (52% male, mean age and FEV1, 72 years and 35% predicted) were enrolled. 4MGS and baseline demographics were recorded at hospital discharge. All-cause readmission and mortality were collected for 1 y after discharge, and multivariable Cox-proportional hazards regression were performed. Kaplan-Meier and Competing risk analysis was conducted comparing time to all-cause readmission and mortality between 4MGS quartiles.111 participants (52%) were readmitted, and 35 (16%) died during the follow-up period. 4MGS was associated with all-cause readmission, with an adjusted subdistribution hazard ratio of 0.868 (95% CI 0.797-0.945; p=0.001) per 0.1 m·s-1 increase in gait speed, and with all-cause mortality with an adjusted subdistribution hazard ratio of 0.747 (95% CI: 0.622-0.898; p=0.002) per 0.1 m·s-1 increase in gait speed. Readmission and mortality models incorporating 4MGS had higher discrimination than age or FEV1% predicted alone, with areas under the receiver operator characteristic curves of 0.73 and 0.80 respectively. Kaplan-Meier and Competing Risk curves demonstrated that those in slower gait speed quartiles had reduced time to readmission and mortality (log rank both p<0.001).4MGS provides a simple means of identifying at-risk patients with COPD at hospital discharge. This provides valuable information to plan post-discharge care and support.

Journal article

van der Plaat D, Madan I, Coggon D, van Tongeren M, Edge R, Muiry R, Parsons V, Cullinan Pet al., 2021, Occupational risks of COVID-19 in NHS workers in England, Publisher: medRxiv

Objective To quantify occupational risks of Covid-19 among healthcare staff during the first wave of the pandemic in EnglandMethods Using pseudonymised data on 902,813 individuals continuously employed by 191 National Health Service trusts during 1.1.19 to 31.7.20, we explored demographic and occupational risk factors for sickness absence ascribed to Covid-19 during 9.3.20 to 31.7.20 (n = 92,880). We estimated odds ratios (ORs) by multivariate logistic regression.Results With adjustment for employing trust, demographic characteristics, and previous frequency of sickness absence, risk relative to administrative/clerical occupations was highest in additional clinical services (a group that included care assistants) (OR 2.31), registered nursing and midwifery professionals (OR 2.28) and allied health professionals (OR 1.94), and intermediate in doctors and dentists (OR 1.55). Differences in risk were higher after the employing trust had started to care for documented Covid-19 patients, and were reduced, but not eliminated, following additional adjustment for exposure to infected patients or materials, assessed by a job-exposure matrix. For prolonged Covid-19 sickness absence (episodes lasting >14 days), the variation in risk by staff group was somewhat greater.Conclusions After allowance for possible bias and confounding by non-occupational exposures, we estimated that relative risks for Covid-19 among most patient-facing occupations were between 1.5 and 2.5. The highest risks were in those working in additional clinical services, nursing and midwifery and in allied health professions. Better protective measures for these staff groups should be a priority. Covid-19 may meet criteria for compensation as an occupational disease in some healthcare occupations.

Working paper

Edge R, van der Plaat D, Parsons V, Coggon D, van Tongeren M, Muiry R, Madan I, Cullinan Pet al., 2021, Changing patterns of sickness absence among healthcare workers in England during the COVID-19 pandemic, Publisher: medRxiv

Objective To explore impacts of the COVID-19 pandemic on patterns of sickness absence among staff employed by the National Health Service (NHS) in England.Methods We analysed prospectively collected, pseudonymised data on 959,356 employees who were continuously employed by NHS trusts during 1 January 2019 to 31 July 2020, comparing the frequency of new sickness absence in 2020 with that at corresponding times in 2019.Results After exclusion of episodes directly related to COVID-19, the overall incidence of sickness absence during the initial 10 weeks of the pandemic (March-May 2020) was more than 20% lower than in corresponding weeks of 2019, but trends for specific categories of illness varied. Marked increases were observed for asthma (122%), infectious diseases (283%) and mental illness (42.3%), while reductions were apparent for gastrointestinal problems (48.4%), genitourinary/gynaecological disorders (33.8%), eye problems (42.7%), injury and fracture (27.7%), back problems (19.6%), other musculoskeletal disorders (29.3%), disorders of ear, nose and throat (32.7%), cough/flu (24.5%) and cancer (24.1%). A doubling of new absences for pregnancy-related disorders during 18 May to 19 July of 2020 was limited to women with earlier COVID-19 sickness absence.Conclusions Various factors will have contributed to the large and divergent changes that were observed. The findings add to concerns regarding delays in diagnosis and treatment of cancers, and support a need to plan for a large backlog of treatment for many other diseases. Further research should explore the rise in absence for pregnancy-related disorders among women with earlier COVID-19 sickness absence.

Working paper

Wiszniewska M, Dellis P, van Kampen V, Suojalehto H, Munoz X, Walusiak-Skorupa J, Lindstrom I, Merget R, Romero-Mesones C, Sastre J, Quirce S, Mason P, Rifflart C, Godet J, de Blay F, Vandenplas Oet al., 2021, Characterization of Occupational Eosinophilic Bronchitis in a Multicenter Cohort of Subjects with Work-Related Asthma Symptoms, JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE, Vol: 9, Pages: 937-+, ISSN: 2213-2198

Journal article

Bloom C, Tom D, Docherty A, Lipworth B, Johnston S, Nguyen-Van-Tam J, Carson G, Dunning J, Harrison E, Baillie K, Semple M, Cullinan P, Openshaw Pet al., 2021, Risk of adverse outcomes in patients with underlying respiratory conditions hospitalised with COVID-19 using the ISARIC WHO Clinical Characterisation Protocol: a national, multicentre prospective cohort, The Lancet Respiratory Medicine, ISSN: 2213-2600

BackgroundStudies of hospitalised COVID-19 patients have found inconsistencies in mortality associated with underlying respiratory conditions and inhaled corticosteroid (ICS) use. We sought to investigate this relationship using a national, multicentre, prospective cohort. MethodsProspective, multicentre UK cohort of hospitalised COVID-19 patients. Patients with asthma, chronic pulmonary disease (CPD), or both, were identified and stratified by age (years): <16, 16-49 and ≥50. In-hospital mortality was measured using multilevel Cox proportional hazards, adjusting for demographics, comorbidities and medications (ICS, short-acting-beta-agonists (SABA), long-acting-beta-agonists (LABA)). Asthma patients using ICS+LABA+another asthma medication were considered ‘severe’.Findings75,463 patients were included: <16 years, 860 patients (8.6% asthma); 16-49 years, 8,950 patients (20.9% asthma), ≥50 years, 65,653 patients (9.0% asthma, 15.6% CPD, 3.2% asthma & CPD). Asthma patients were significantly more likely to receive critical care, CPD patients were significantly less likely to. In patients 16-49 years, only those with severe asthma had a significant increase in mortality (adjusted HR (95%CI): no therapy=1.21 (0.78-1.88), SABA-only=1.03 (0.66-1.62), ICS-only=1.01 (0.68-1.51), ICS+LABA=1.06 (0.70-1.61), severe=2.07 (1.35-3.18)). In patients ≥50 years, there was increased mortality associated with CPD and severe asthma. ICS use was associated with lower mortality (adjusted HR (95% CI): asthma+no_ICS=0.97 (0.90-1.04), asthma+ICS=0.87 (0.81-0.93), CPD+no_ICS=1.16 (1.11-1.21), CPD+ICS=1.10 (1.04-1.17), asthma+CPD+no_ICS=1.13 (1.00-1.27), asthma+CPD+ICS=0.98 (0.89-1.07).InterpretationUnderlying respiratory conditions are common in hospitalised COVID-19 patients. Regardless of admission severity and comorbidities, asthma patients were more likely to receive critical care than patients without underlying respiratory disease; CPD patients were less

Journal article

Reynolds C, Feary J, Cullinan P, 2020, Occupational contributions to interstitial lung disease, Clinics in Chest Medicine, Vol: 41, Pages: 697-707, ISSN: 0272-5231

Journal article

Coggon D, Croft P, Cullinan P, Williams ANet al., 2020, Discussion on Covid age reply, OCCUPATIONAL MEDICINE-OXFORD, Vol: 70, Pages: 687-688, ISSN: 0962-7480

Journal article

Cullinan P, Vandenplas O, Bernstein D, 2020, Assessment and management of occupational asthma, Journal of Allergy and Clinical Immunology: In Practice, Vol: 8, Pages: 3264-3276, ISSN: 2213-2198

Exposures at work can give rise to different phenotypes of “work-related asthma.” The focus of this review is on the diagnosis and management of sensitizer-induced occupational asthma (OA) caused by either a high- or low-molecular-weight agent encountered in the workplace. The diagnosis of OA remains a challenge for the clinician because there is no simple test with a sufficiently high level of accuracy. Instead, the diagnostic process combines different procedures in a stepwise manner. These procedures include a detailed clinical history, immunologic testing, measurement of lung function parameters and airway inflammatory markers, as well as various methods that relate changes in these functional and inflammatory indices to workplace exposure. Their diagnostic performances, alone and in combination, are critically reviewed and summarized into evidence-based key messages. A working diagnostic algorithm is proposed that can be adapted to the suspected agent, purpose of diagnosis, and available resources. Current information on the management options of OA is summarized to provide pragmatic guidance to clinicians who have to advise their patients with OA.

Journal article

Bennett AN, Dyball DM, Boos CJ, Fear NT, Schofield S, Bull AMJ, Cullinan P, ADVANCE Studyet al., 2020, Study protocol for a prospective, longitudinal cohort study investigating the medical and psychosocial outcomes of UK combat casualties from the Afghanistan war: the ADVANCE Study., BMJ Open, Vol: 10, Pages: 1-11, ISSN: 2044-6055

INTRODUCTION: The Afghanistan war (2003-2014) was a unique period in military medicine. Many service personnel survived injuries of a severity that would have been fatal at any other time in history; the long-term health outcomes of such injuries are unknown. The ArmeD SerVices TrAuma and RehabilitatioN OutComE (ADVANCE) study aims to determine the long-term effects on both medical and psychosocial health of servicemen surviving this severe combat related trauma. METHODS AND ANALYSIS: ADVANCE is a prospective cohort study. 1200 Afghanistan-deployed male UK military personnel and veterans will be recruited and will be studied at 0, 3, 6, 10, 15 and 20 years. Half are personnel who sustained combat trauma; a comparison group of the same size has been frequency matched based on deployment to Afghanistan, age, sex, service, rank and role. Participants undergo a series of physical health tests and questionnaires through which information is collected on cardiovascular disease (CVD), CVD risk factors, musculoskeletal disease, mental health, functional and social outcomes, quality of life, employment and mortality. ETHICS AND DISSEMINATION: The ADVANCE Study has approval from the Ministry of Defence Research Ethics Committee (protocol no:357/PPE/12) agreed 15 January 2013. Its results will be disseminated through manuscripts in clinical/academic journals and presentations at professional conferences, and through participant and stakeholder communications. TRIAL REGISTRATION NUMBER: The ADVANCE Study is registered at ISRCTN ID: ISRCTN57285353.

Journal article

van der Plaat DA, De Matteis S, Sadhra S, Jarvis D, Cullinan P, Minelli Cet al., 2020, Interaction between occupational exposures and antioxidant geneson chronic obstructive pulmonary disease in UK Biobank, ERS, Publisher: European Medical Group LTD, Pages: 77-78, ISSN: 2054-3166

Conference paper

Coggon D, Croft P, Cullinan P, Williams Aet al., 2020, Assessment of workers' personal vulnerability to covid-19 using 'covid-age'., Occupational Medicine, Vol: 70, Pages: 461-464, ISSN: 0962-7480

Journal article

Feary J, Cannon J, Fitzgerald B, Szram J, Schofield S, Cullinan Pet al., 2020, Follow-up survey of patients with occupational asthma., Occupational Medicine, Vol: 70, Pages: 231-234, ISSN: 0962-7480

BACKGROUND: Occupational asthma (OA) is often associated with a poor prognosis and the impact of a diagnosis on an individual's career and income can be significant. AIMS: We sought to understand the consequences of a diagnosis of OA to patients attending our clinic. METHODS: Using a postal questionnaire, we surveyed all patients attending our specialist occupational lung disease clinic 1 year after having received a diagnosis of OA due to a sensitizer (n = 125). We enquired about their current health and employment status and impact of their diagnosis on various aspects of their life. Additional information was collected by review of clinical records. RESULTS: We received responses from 71 (57%) patients; 77% were referred by an occupational health (OH) provider. The median duration of symptoms prior to referral was 18 months (interquartile range (IQR) 8-48). At 1 year, 79% respondents were no longer exposed to the causal agent. Whilst the unexposed patients reported an improvement in symptoms compared with those still exposed (82% versus 53%; P = 0.023), they had poorer outcomes in terms of career, income and how they felt treated by their employer; particularly those not currently employed. Almost all (>90%) of those still employed had been referred by an OH provider compared with 56% of those currently unemployed (P = 0.002)x. CONCLUSIONS: The negative impact of OA on people's careers, livelihood and quality of life should not be underestimated. However, with early detection and specialist care, the prognosis is often good and particularly so for those with access to occupational health.

Journal article

Mueller W, Cowie H, Horwell CJ, Baxter PJ, McElvenny D, Booth M, Cherrie JW, Cullinan P, Jarvis D, Ugartef C, Inoue Het al., 2020, Standardized epidemiological protocols for populations affected by volcanic eruptions, Bulletin of the World Health Organization, Vol: 98, Pages: 362-364, ISSN: 0042-9686

Journal article

Suojalehto H, Suuronen K, Cullinan P, Lindström I, Sastre J, Walusiak-Skorupa J, Munoz X, Talini D, Klusackova P, Moore V, Merget R, Svanes C, Mason P, dell'Omo M, Moscato G, Quirce S, Hoyle J, Sherson D, Preisser A, Seed M, Rifflart C, Godet J, de Blay F, Vandenplas O, European Network for the Phenotyping of Occupational Asthma E-PHOCAS investigatorset al., 2020, Phenotyping occupational asthma caused by acrylates in a multicenter cohort study, Journal of Allergy and Clinical Immunology: In Practice, Vol: 8, Pages: 971-979.e1, ISSN: 2213-2198

BACKGROUND: While acrylates are well-known skin sensitizers, they are not classified as respiratory sensitizers although several cases of acrylate-induced occupational asthma (OA) have been reported. OBJECTIVE: To evaluate the characteristics of acrylate-induced OA in a large series of cases and compare those with OA induced by other low-molecular-weight (LMW) agents. METHODS: Jobs and exposures, clinical and functional characteristics, and markers of airway inflammation were analyzed in an international, multicenter, retrospective cohort of subjects with OA ascertained by a positive inhalation challenge to acrylates (n = 55) or other LMW agents (n = 418) including isocyanates (n = 125). RESULTS: Acrylate-containing glues were the most prevalent products, and industrial manufacturing, dental work, and beauty care were typical occupations causing OA. Work-related rhinitis was more common in acrylate-than in isocyanate-induced asthma (P < .001). The increase in postchallenge fractional exhaled nitric oxide was significantly greater in acrylate-induced OA (26.0; 8.2 to 38.0 parts per billion [ppb]) than in OA induced by other LMW agents (3.0; -1.0 to 10.0 ppb; P < .001) or isocyanates (5.0; 2.0 to 16.0 ppb; P = .010). Multivariable models confirmed that OA induced by acrylates was significantly and independently associated with a postchallenge increase in fractional exhaled nitric oxide (≥17.5 ppb). CONCLUSIONS: Acrylate-induced OA shows specific characteristics, concomitant work-related rhinitis, and exposure-related increases in fractional exhaled nitric oxide, suggesting that acrylates may induce asthma through different immunologic mechanisms compared with mechanisms through which other LMW agents may induce asthma. Our findings reinforce the need for a reevaluation of the hazard classification of acrylates, and further investigation of the pathophysiological mechanisms underlying their respiratory sensitizing potential.

Journal article

Preston GW, Dagnino S, Ponzi E, Sozeri O, van Veldhoven K, Barratt B, Liu S, Grigoryan H, Lu SS, Rappaport SM, Chung KF, Cullinan P, Sinharay R, Kelly FJ, Chadeau-Hyam M, Vineis P, Phillips DHet al., 2020, Relationships between airborne pollutants, serum albumin adducts and short-term health outcomes in an experimental crossover study, Chemosphere, Vol: 239, ISSN: 1879-1298

Exposure to air pollution can have both short-term and long-term effects on health. However, the relationships between specific pollutants and their effects can be obscured by characteristics of both the pollution and the exposed population. One way of elucidating the relationships is to link exposures and internal changes at the level of the individual. To this end, we combined personal exposure monitoring (59 individuals, Oxford Street II crossover study) with mass-spectrometry-based analyses of putative serum albumin adducts (fixed-step selected reaction monitoring). We attempted to infer adducts' identities using data from another, higher-resolution mass spectrometry method, and were able to detect a semi-synthetic standard with both methods. A generalised least squares regression method was used to test for associations between amounts of adducts and pollution measures (ambient concentrations of nitrogen dioxide and particulate matter), and between amounts of adducts and short-term health outcomes (measures of lung health and arterial stiffness). Amounts of some putative adducts (e.g., one with a positive mass shift of approximately 143Da) were associated with exposure to pollution (11 associations), and amounts of other adducts were associated with health outcomes (eight associations). Adducts did not appear to provide a link between exposures and short-term health outcomes.

Journal article

Ratanachina J, De Matteis S, Cullinan P, Burney Pet al., 2019, Pesticide exposure and lung function: a systematic review and meta-analysis., Occupational Medicine, Vol: 70, Pages: 14-23, ISSN: 0962-7480

BACKGROUND: Epidemiological studies have reported associations between pesticide exposure and respiratory health effects, but the quantitative impact on lung function is unclear. To fill this gap, we undertook a systematic review of the available literature on the association between pesticide exposure and pulmonary function. AIMS: To examine all available literature regarding the relationship between occupational and environmental exposure to pesticides and lung function. METHODS: We searched MEDLINE, EMBASE and Web of Science databases to 1 October 2017 without any date or language restrictions using a combination of MeSH terms and free text for 'pesticide exposure' and 'lung function'. We included studies that met the criteria of our research protocol registered in PROSPERO, and we assessed their quality using a modified Newcastle-Ottawa scale. RESULTS: Of 2356 articles retrieved, 56 articles were included in the systematic review and pooled in meta-analyses for forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC), FVC and FEV1. There was tentative evidence that exposure to cholinesterase (ChE) inhibiting pesticides reduced FEV1/FVC and no evidence that paraquat exposure affected lung function in farmers. CONCLUSIONS: Respiratory surveillance should be enhanced in those exposed to ChE-inhibiting pesticides which reduced FEV1/FVC according to the meta-analysis. Our study is limited by heterogeneity between studies due to different types of exposure assessment to pesticides and potential confounders. Further studies with a more accurate exposure assessment are suggested.

Journal article

Nafees AA, De Matteis S, Kadir MM, Burney P, Coggon D, Semple S, Cullinan Pet al., 2019, MultiTex RCT - a multifaceted intervention package for protection against cotton dust exposure among textile workers - a cluster randomized controlled trial in Pakistan: study protocol, Trials, Vol: 20, ISSN: 1745-6215

BACKGROUND: In the Pakistani textile industry the prevalence of workplace respiratory illnesses, including byssinosis, is high. The MultiTex RCT study aims to determine the effectiveness of a multifaceted intervention package in reducing dust levels in cotton mills, decreasing the frequency of respiratory symptoms among cotton textile workers, and improving their lung function. METHODS/DESIGN: We will conduct a cluster-randomized controlled trial at 28 textile mills in Karachi. The intervention will comprise: training in occupational health for all workers and managers reinforced by regular refresher sessions; the formation of workplace committees to draw up, agree and promote a health and safety plan that includes wet mopping, safe disposal of cotton dust, and the use of simple face-masks, as well as further publicity about the risks from cotton dust; and provision of adequate supplies of face-masks to support the health and safety plan. Participating mills will be randomized to intervention and control arms following a baseline survey. The impact of the intervention will be determined through follow-up surveys conducted at 3, 12 and 18 months. Data collection in the surveys will include spirometry, questionnaire-based interviews and cotton-dust measurements. DISCUSSION: If successful, the study may pave the way for simple, low-cost interventions that can help reduce cotton-dust levels in textile mills, and improve the respiratory health of textile workers in developing countries such as Pakistan. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT03738202. Registered on 12 November 2018.

Journal article

Haider S, Nakamura T, Colicino S, Murray C, Holloway J, Simpson A, Cullinan P, Custovic Aet al., 2019, Different definitions of atopic dermatitis: Impact on prevalence estimates and associated risk factors, British Journal of Dermatology, Vol: 181, Pages: 1272-1279, ISSN: 1365-2133

BackgroundThere is no objective test that can unequivocally confirm the diagnosis of atopic dermatitis (AD), and no uniform clinical definition.ObjectiveTo investigate to what extent operational definitions of AD cause fluctuation in the prevalence estimates and the associated risk factors.MethodsWe first reviewed operational definitions of AD used in the literature. We then tested the impact of the choice of the most common definitions of “Cases” and “Controls” on AD prevalence estimates and associated risk factors (including filaggrin‐FLG mutations) among children aged 5 years in two population‐based birth cohorts: Manchester Asthma and Allergy Study (MAAS) and Asthma in Ashford. Model performance was measured by the percentage of children within an area of clinical indecision (defined as having a posterior probability of AD between 25% and 60%).ResultsWe identified 59 different definitions of AD across 45 reviewed studies. Of those, we chose 4 common “Case” definitions, and 2 definitions of “Controls”. The prevalence estimates using different case definitions ranged between 22% and 33% in MAAS, and 12% and 22% in Ashford. The area of clinical indecision ranged from 32% to 44% in MAAS, and from 9% to 29% in Ashford. Depending on the case definition used, the associations with FLG mutations varied (ORs [95% CI]: 1.8 [1.1‐2.9] to 2.2 [1.3‐3.7] (MAAS) and 1.7 [0.8‐3.7] to 2.3 [1.2‐4.5] (Ashford)). Associations with FLG mutations also differed when using the same “Case” definition, but different definitions of “Controls”.ConclusionUse of different definitions of AD results in substantial difference in prevalence estimates, the performance of prediction models, and association with risk factors.

Journal article

Kwan HY, Maddocks M, Nolan CM, Jones SE, Patel S, Barker RE, Kon SSC, Polkey MI, Cullinan P, Man WD-Cet al., 2019, The prognostic significance of weight loss in chronic obstructive pulmonary disease-related cachexia: a prospective cohort study., Journal of Cachexia, Sarcopenia and Muscle, Vol: 10, Pages: 1330-1338, ISSN: 2190-6009

BACKGROUND: Cachexia is an important extra-pulmonary manifestation of chronic obstructive pulmonary disease (COPD) presenting as unintentional weight loss and altered body composition. Previous studies have focused on the relative importance of body composition compared with body mass rather than the relative importance of dynamic compared with static measures. We aimed to determine the prevalence of cachexia and pre-cachexia phenotypes in COPD and examine the associations between cachexia and its component features with all-cause mortality. METHODS: We enrolled 1755 consecutive outpatients with stable COPD from two London centres between 2012 and 2017, stratified according to European Respiratory Society Task Force defined cachexia [unintentional weight loss >5% and low fat-free mass index (FFMI)], pre-cachexia (weight loss >5% but preserved FFMI), or no cachexia. The primary outcome was all-cause mortality. We calculated hazard ratios (HRs) using Cox proportional hazards regression for cachexia classifications (cachexia, pre-cachexia, and no cachexia) and component features (weight loss and FFMI) and mortality, adjusting for age, sex, body mass index, and disease-specific prognostic markers. RESULTS: The prevalence of cachexia was 4.6% [95% confidence interval (CI): 3.6-5.6] and pre-cachexia 1.6% (95% CI: 1.0-2.2). Prevalence was similar across sexes but increased with worsening Global Initiative for Chronic Obstructive Pulmonary Disease spirometric stage and Medical Research Council dyspnoea score (all P < 0.001). There were 313 (17.8%) deaths over a median (interquartile range) follow-up duration 1089 (547-1704) days. Both cachexia [HR 1.98 (95% CI: 1.31-2.99), P = 0.002] and pre-cachexia [HR 2.79 (95% CI: 1.48-5.29), P = 0.001] were associated with increased mortality. In multivariable analysis, the unintentional weight loss feature of cachexia was independently associated with mortality [HR 2.16 (95% CI: 1.31-3.08), P&nbs

Journal article

Schofield SJ, Woods A, Szram J, Newman Taylor AJ, Cullinan Pet al., 2019, COPD and breathlessness in older workers predict economic inactivity; A prospective cohort study, American Journal of Respiratory and Critical Care Medicine, Vol: 200, Pages: 1228-1233, ISSN: 1073-449X

RATIONALE: There is an aspiration to retain increasing numbers of older workers in employment and strategies to achieve this need to make provision for the increasing prevalence of chronic diseases with age. There is a consistent body of cross-sectional evidence that suggests that patients with chronic obstructive pulmonary disease are more likely to have adverse employment outcomes. OBJECTIVES: We report the findings of the first longitudinal study of this issue. METHODS: We recruited full-time employed men and women in their 50's and followed them for a period of 18 months; we examined, after adjustment for potential confounders, the associations between breathlessness and airway obstruction at baseline and loss of employment in the intervening period. MEASUREMENTS AND MAIN RESULTS: Among participants responding to the follow up questionnaire (1656/1773 (93%)), the majority (78.5%) continued in full-time employment, but 10.6% were in part-time employment and 10.9% were no longer in paid employment. The adjusted risk of loss of employment was significantly increased for those with moderate or severe chronic obstructive pulmonary disease (RR 2.89, 95% ci 1.80-4.65) or breathlessness (3.07, 2.16-4.37) at baseline. There was no evident modification by sex or by manual/non-manual work. CONCLUSIONS: Airway obstruction and breathlessness are independently associated with premature loss from the workforce in older workers; these observations provide strong support to the available cross-sectional evidence and suggest that interventions to help those with chronic obstructive pulmonary disease who wish to remain in work need to be tested.

Journal article

Reynolds CJ, Minelli C, Darnton A, Cullinan Pet al., 2019, Mesothelioma mortality in Great Britain: how much longer will dockyards dominate?, Occupational and Environmental Medicine, Vol: 76, Pages: 908-912, ISSN: 1351-0711

OBJECTIVES: We aimed to investigate whether there has been a geographic shift in the distribution of mesothelioma deaths in Great Britain given the decline of shipbuilding and progressive exposure regulation. METHODS: We calculated age-adjusted mesothelioma mortality rates and estimated rate ratios for areas with and without a dockyard. We compared spatial autocorrelation statistics (Moran's I) for age-adjusted rates at local authority district level for 2002-2008 and 2009-2015. We measured the mean distance of the deceased's postcode to the nearest dockyard at district level and calculated the association of average distance to dockyard and district mesothelioma mortality using simple linear regression for men, for 2002-2008 and 2009-2015. RESULTS: District age-adjusted male mortality rates fell during 2002-2015 for 80 of 348 districts (23%), rose for 267 (77%) and were unchanged for one district; having one or more dockyards in a district was associated with rates falling (OR=2.43, 95% CI 1.22 to 4.82, p=0.02). The mortality rate ratio for men in districts with a dockyard, compared with those without a dockyard was 1.41 (95% CI 1.35 to 1.48, p<0.05) for 2002-2008 and 1.18 (95% CI 1.13 to 1.23, p<0.05) for 2009-2015. Spatial autocorrelation (measured by Moran's I) decreased from 0.317 (95% CI 0.316 to 0.319, p=0.001) to 0.312 (95% CI 0.310 to 0.314, p=0.001) for men and the coefficient of the association between distance to dockyard and district level age-adjusted male mortality (per million population) from -0.16 (95% CI -0.21 to -0.10, p<0.01) to -0.13 (95% CI -0.18 to -0.07, p<0.01) for men, when comparing 2002-2008 with 2009-2015. CONCLUSION: For most districts age-adjusted mesothelioma mortality rates increased through 2002-2015 but the relative contribution from districts with a dockyard fell. Dockyards remain strongly spatially associated with mesothelioma mortality but the strength of this association appears to be falling and mesotheliom

Journal article

Brock Jacobsen I, Baelum J, Carstensen O, Skadhauge LR, Feary J, Cullinan P, Sherson DLet al., 2019, Delayed occupational asthma from epoxy exposure., Occup Med (Lond), Vol: 69, Pages: 511-514

BACKGROUND: A delayed asthma reaction occurring several hours after exposure is difficult to diagnose. AIMS: To confirm a delayed asthma reaction in five workers following epoxy exposure. CASE REPORT: Working conditions with exposure to epoxy encountered at the workplace were reproduced in a challenge chamber. Specific inhalation challenge (SIC) with epoxy was compared to a control challenge. All five cases had delayed a asthma response 6-15 h after epoxy exposure. CONCLUSIONS: Our study confirms that SIC is a useful tool in diagnosing delayed asthma response.

Journal article

Archangelidi O, Carr SB, Simmonds NJ, Bilton D, Banya W, Cullinan Pet al., 2019, Non-invasive ventilation and clinical outcomes in cystic fibrosis: Findings from the UK CF registry, Journal of Cystic Fibrosis, Vol: 18, Pages: 665-670, ISSN: 1569-1993

Background: Non-invasive ventilation (NIV) for respiratory failure and airway clearance is an established intervention in cystic fibrosis (CF), but its therapeutic benefit on lung function and survival remains under-investigated. Methods: Using data from the UK CF Registry between 2007 and 2015, we explored the patterns of NIV use, and assessed changes in mean percent predicted FEV1 (ppFEV1) prior to and after NIV use, and the survival of patients on NIV. Results: Among 11,079 patients, 1107 had at least one record of NIV treatment. Incidence and prevalence of NIV was lower in children and followed non-linear temporal patterns. Adjusting for other risk factors, ppFEV1 rose by 0.70 (95%CI: -0.83, 2.24) after first NIV use in children. In adults with a low ppFEV1 (<40%) at initiation of treatment, NIV increased mean ppFEV1 by 2.60 (95% CI: 0.93, 4.27). Our analysis showed that NIV initiation is associated with an increased risk of death/transplant in both children (HR = 2.47; 95%CI: 1.20–5.08) and adults (HR = 1.96; 95% CI: 1.63–2.36) but effect was attenuated in children with low ppFEV1 (<40%). Conclusions: NIV usage in CF improves spirometric values but does not benefit survival. Further studies are required to better understand survival outcomes and ultimately improve NIV outcomes in CF.

Journal article

Vandenplas O, Godet J, Hurdubaea L, Rifflart C, Suojalehto H, Walusiak-Skorupa J, Munoz X, Sastre J, Klusackova P, Moore V, Merget R, Talini D, Kirkeleit J, Mason P, Folletti I, Cullinan P, Moscato G, Quirce S, Hoyle J, Sherson D, Kauppi P, Preisser A, Meyer N, de Blay F, European network for the PHenotyping of OCcupational ASthma E-PHOCAS investigatorset al., 2019, Severe occupational asthma: insights from a multicenter European cohort, Journal of Allergy and Clinical Immunology: In Practice, Vol: 7, Pages: 2309-2318.e4, ISSN: 2213-2198

BACKGROUND: Although sensitizer-induced occupational asthma (OA) accounts for an appreciable fraction of adult asthma, the severity of OA has received little attention. OBJECTIVE: The aim of this study was to characterize the burden and determinants of severe OA in a large multicenter cohort of subjects with OA. METHODS: This retrospective study included 997 subjects with OA ascertained by a positive specific inhalation challenge completed in 20 tertiary centers in 11 European countries during the period 2006 to 2015. Severe asthma was defined by a high level of treatment and any 1 of the following criteria: (1) daily need for a reliever medication, (2) 2 or more severe exacerbations in the previous year, or (3) airflow obstruction. RESULTS: Overall, 162 (16.2%; 95% CI, 14.0%-18.7%) subjects were classified as having severe OA. Multivariable logistic regression analysis revealed that severe OA was associated with persistent (vs reduced) exposure to the causal agent at work (odds ratio [OR], 2.78; 95% CI, 1.50-5.60); a longer duration of the disease (OR, 1.04; 95% CI, 1.00-1.07); a low level of education (OR, 2.69; 95% CI, 1.73-4.18); childhood asthma (OR, 2.92; 95% CI, 1.13-7.36); and sputum production (OR, 2.86; 95% CI, 1.87-4.38). In subjects removed from exposure, severe OA was associated only with sputum production (OR, 3.68; 95% CI, 1.87-7.40); a low education level (OR, 3.41; 95% CI, 1.72-6.80); and obesity (OR, 1.98; 95% CI, 0.97-3.97). CONCLUSIONS: This study indicates that a substantial proportion of subjects with OA experience severe asthma and identifies potentially modifiable risk factors for severe OA that should be targeted to reduce the adverse impacts of the disease.

Journal article

Suojalehto H, Suuronen K, Cullinan P, 2019, Specific challenge testing for occupational asthma: revised handbook, European Respiratory Journal, Vol: 54, ISSN: 0903-1936

pecific inhalation challenge is considered a reference standard in the diagnosis of occupational asthma. An updated handbook of challenge techniques for a large number of sensitising agents from 11 European centres is now available. http://bit.ly/2XVpW1P

Journal article

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