Lynn Josephs

Community study of role of viral infections in exacerbations of asthma in 9-11 year old children.

Abstract Objective: To study the association between upper and lower respiratory viral infections and acute exacerbations of asthma in schoolchildren in the community. Design: Community based 13 month longitudinal study using diary card respiratory symptom and peak expiratory flow monitoring to allow early sampling for viruses. Subjects: 108 Children aged 9-11 years who had reported wheeze or cough, or both, in a questionnaire. Setting: Southampton and surrounding community. Main outcome measures: Upper and lower respiratory viral infections detected by polymerase chain reaction or conventional methods, reported exacerbations of asthma, computer identified episodes of respiratory tract symptoms or peak flow reductions. Results: Viruses were detected in 80% of reported episodes of reduced peak expiratory flow, 80% of reported episodes of wheeze, and in 85% of reported episodes of upper respiratory symptoms, cough, wheeze, and a fall in peak expiratory flow. The median duration of reported falls in peak expiratory flow was 14 days, and the median maximum fall in peak expiratory flow was 81 1/min. The most commonly identified virus type was rhinovirus. Conclusions: This study supports the hypothesis that upper respiratory viral infections are associated with 80-85% of asthma exacerbations in school age children. Key messages Key messages In this study common cold viruses were found in 80-85% of reported exacerbations of asthma in children Rhinoviruses, which cause most common colds, accounted for two thirds of viruses detected Analysis of diary cards also showed large numbers of similar but less severe episodes that may also be viral in origin

Personal exposure to nitrogen dioxide and risk of airflow obstruction in asthmatic children with upper respiratory infection

BACKGROUND Several studies have linked air pollution by nitrogen dioxide (NO2) with increased hospital admissions for asthma in children. Exacerbations of asthma in children are often precipitated by upper respiratory infections. It is therefore possible that NO2increases the risk of airways obstruction when asthmatic children develop upper respiratory infections. METHODS To test this hypothesis a sample of 114 asthmatic children aged 7–12 years were followed for a total of up to 13 months. Probable upper respiratory infections were identified by consensus review of daily symptom diaries, and episodes of airways obstruction from serial records of peak expiratory flow (PEF). Personal exposures to NO2 were measured with Palmes tubes that were changed weekly. Generalised estimating equations were used to assess the relative risk (RR) of an asthmatic exacerbation starting within seven days of an upper respiratory infection according to estimated NO2 exposure during the one week period from two days before to four days after the onset of the infection. RESULTS The children were followed for an average of 34 weeks during which 318 upper respiratory infections and 224 episodes of reduced PEF were diagnosed. PEF episodes were much more likely to occur in the seven days following the onset of an upper respiratory infection than at other times. Estimated exposures to NO2 at the time of infections were generally low (geometric mean 10.6 μg/m3). Compared with exposures of ⩽8 μg/m3, exposures of >28 μg/m3 were associated with a RR of 1.9 (95% confidence interval 1.1 to 3.4) for the development of an asthmatic episode within seven days of an infection. CONCLUSIONS The findings give some support to the hypothesis that NO2increases the risk of asthmatic exacerbations following respiratory infections, even at relatively low levels of exposure. Further studies in populations with higher exposures would be useful.

Identifying Risk of Future Asthma Attacks Using UK Medical Record Data: A Respiratory Effectiveness Group Initiative

BACKGROUND Asthma attacks are common, serious, and costly. Individual factors associated with attacks, such as poor symptom control, are not robust predictors. OBJECTIVE We investigated whether the rich data available in UK electronic medical records could identify patients at risk of recurrent attacks. METHODS We analyzed anonymized, longitudinal medical records of 118,981 patients with actively treated asthma (ages 12-80 years) and 3 or more years of data. Potential risk factors during 1 baseline year were evaluated using univariable (simple) logistic regression for outcomes of 2 or more and 4 or more attacks during the following 2-year period. Predictors with significant univariable association (P < .05) were entered into multiple logistic regression analysis with backward stepwise selection of the model including all significant independent predictors. The predictive accuracy of the multivariable models was assessed. RESULTS Independent predictors associated with future attacks included baseline-year markers of attacks (acute oral corticosteroid courses, emergency visits), more frequent reliever use and health care utilization, worse lung function, current smoking, blood eosinophilia, rhinitis, nasal polyps, eczema, gastroesophageal reflux disease, obesity, older age, and being female. The number of oral corticosteroid courses had the strongest association. The final cross-validated models incorporated 19 and 16 risk factors for 2 or more and 4 or more attacks over 2 years, respectively, with areas under the curve of 0.785 (95% CI, 0.780-0.789) and 0.867 (95% CI, 0.860-0.873), respectively. CONCLUSIONS Routinely collected data could be used proactively via automated searches to identify individuals at risk of recurrent asthma attacks. Further research is needed to assess the impact of such knowledge on clinical prognosis.

Managing patients with stable respiratory disease planning air travel: a primary care summary of the British Thoracic Society recommendations

Air travel poses medical challenges to passengers with respiratory disease, principally because of exposure to a hypobaric environment. In 2002 the British Thoracic Society published recommendations for adults and children with respiratory disease planning air travel, with a web update in 2004. New full recommendations and a summary were published in 2011, containing key recommendations for the assessment of high-risk patients and identification of those likely to require in-flight supplemental oxygen. This paper highlights the aspects of particular relevance to primary care practitioners with the following key points: (1) At cabin altitudes of 8000 feet (the usual upper limit of in-flight cabin pressure, equivalent to 0.75 atmospheres) the partial pressure of oxygen falls to the equivalent of breathing 15.1% oxygen at sea level. Arterial oxygen tension falls in all passengers; in patients with respiratory disease, altitude may worsen preexisting hypoxaemia. (2) Altitude exposure also influences the volume of any air in cavities, where pressure x volume remain constant (Boyles law), so that a pneumothorax or closed lung bulla will expand and may cause respiratory distress. Similarly, barotrauma may affect the middle ear or sinuses if these cavities fail to equilibrate. (3) Patients with respiratory disease require clinical assessment and advice before air travel to: (a) optimise usual care; (b) consider contraindications to travel and possible need for in-flight oxygen; (c) consider the need for secondary care referral for further assessment; (d) discuss the risk of venous thromboembolism; and (e) discuss forward planning for the journey.

Seasonality, risk factors and burden of community-acquired pneumonia in COPD patients: a population database study using linked health care records

Background Community-acquired pneumonia (CAP) is more common in patients with COPD than in the adult general population, with studies of hospitalized CAP patients consistently reporting COPD as a frequent comorbidity. However, despite an increasing recognition of its importance, large studies evaluating the incidence patterns over time, risk factors and burden of CAP in COPD are currently lacking. Methods A retrospective observational study using a large UK-based database of linked primary and secondary care records was conducted. Patients with a diagnosis of COPD aged ≥40 years were followed up for 5 years from January 1, 2010. CAP and exacerbation episodes were identified from hospital discharge data and primary care coding records, and rates were calculated per month, adjusting for mortality, and displayed over time. In addition, baseline factors predicting future risk of CAP and hospital admission with CAP were identified. Results A total of 14,513 COPD patients were identified: 13.4% (n=1,938) had ≥1 CAP episode, of whom 18.8% suffered from recurrent (≥2) CAP. Highest rates of both CAP and exacerbations were seen in winter. A greater proportion of frequent, compared to infrequent, exacerbators experienced recurrent CAP (5.1% versus 2.0%, respectively, P<0.001); 75.6% of CAP episodes were associated with hospital admission compared to 22.1% of exacerbations. Older age and increasing grade of airflow limitation were independently associated with increased odds of CAP and hospital admission with CAP. Other independent predictors of future CAP included lower body mass index, inhaled corticosteroid use, prior frequent exacerbations and comorbidities, including ischemic heart disease and diabetes. Conclusion CAP in COPD demonstrates clear seasonal patterns, with patient characteristics predictive of the odds of future CAP and hospital admission with CAP. Highlighting this burden of COPD-associated CAP during the winter period informs us of the likely triggers and the need for more effective preventive strategies.

Improved outcomes in ex-smokers with COPD: a UK primary care observational cohort study

Smoking cessation in chronic obstructive pulmonary disease (COPD) reduces accelerated forced expiratory volume in 1 s decline, but impact on key health outcomes is less clear. We studied the relationship of smoking status to mortality and hospitalisation in a UK primary care COPD population. Using patient-anonymised routine data in the Hampshire Health Record Analytical Database, we identified a prevalent COPD cohort, categorising patients by smoking status (current, ex- or never-smokers). Three outcomes were measured over 3 years (2011–2013): all-cause mortality, respiratory-cause unplanned hospital admission and respiratory-cause emergency department attendance. Survival analysis using multivariable Cox regression after multiple imputation was used to estimate hazard ratios for each outcome by smoking status, adjusting for measured confounders (including age, lung function, socioeconomic deprivation, inhaled medication and comorbidities). We identified 16 479 patients with COPD, mean±sd age 70.1±11.1 years. Smoking status was known in 91.3%: 35.1% active smokers, 54.3% ex-smokers, 1.9% never-smokers. Active smokers predominated among younger patients. Compared with active smokers (n=5787), ex-smokers (n=8941) had significantly reduced risk of death, hazard ratio (95% confidence interval) 0.78 (0.70–0.87), hospitalisation, 0.82 (0.74–0.89) and emergency department attendance, 0.78 (0.70–0.88). After adjusting for confounders, ex-smokers had significantly better outcomes, emphasising the importance of effective smoking cessation support, regardless of age or lung function. Many COPD patients smoke: better outcomes in ex-smokers suggest many deaths and admissions avoidable if smokers quit http://ow.ly/l85u30aizmK

P20 A database approach to DOSE score calculation as a tool to identify ‘at risk’ Chronic Obstructive Pulmonary Disease patients through clinical records

Establishing how best to target resources remains a challenge within COPD as this is a heterogeneous patient group with complex needs often poorly reflected by routinely collected clinical measurements such as FEV1. Jones et al. created The DOSE score (dyspnoea (MRC score), obstruction (FEV1 percentage predicted), smoking status and exacerbation number in a year) (Table 1) a validated, clinically useful measure of risk stratification in COPD which utilises data already routinely collected in Primary Care for QOF review.Abstract P20 Table 1 DOSE INDEX SCORING SYSTEM (Jones et al. AJRCCM 2009;180(12):1189–95): The DOSE Index points associated with every category of all four variables are added to build the DOSE Index score By using a collaborative approach with informatics, statistical and clinical input we developed a database approach to calculating a DOSE score using routinely collected and coded Primary and Secondary Care data. A local NHS database holding anonymised clinical records for over one million patients was used to identify a cohort of over 13,000 patients with codes diagnostic of COPD. Microsoft Structured Query Language Server was used to identify, cleanse and standardise the required clinical information and calculate the DOSE score, creating a series of functions that can be replicated across other database management systems. Date of FEV1 percentage predicted was taken as the index date for DOSE score calculation. Where only FEV1 was recorded, a percentage of predicted FEV1 was calculated using available height and age data. Read codes (the routine coding system used in primary care) and ICD-10 codes were used to compile lists identifying those symptoms, diagnoses and prescriptions indicative of COPD exacerbations. These lists were applied in the year prior to the chosen FEV1 value and, functions were written to cluster those events felt to be reflective of a single exacerbation. Read codes reflecting MRC score and smoking status closest in time to the index FEV1 measurement were combined with the above measurements, generating a complete score in approximately 10,000 patients. Partial scores were created for a further 1500 patients with incomplete data for the individual score components. This approach provides a simple way for clinicians to risk stratify their COPD population without increasing their clinical workload. This gives an opportunity to identify those at highest risk of hospital admission and death and proactively allocate resources accordingly.

P31 Copd diagnosis in primary care: a uk observational database study comparing patients with and without confirmed airflow obstruction

Introduction and Objectives COPD is a clinical diagnosis comprising symptoms, risk factors and evidence of post-bronchodilator airflow obstruction (AFO). While spirometry is fundamental to the diagnosis, the National COPD Audit Programme reported in 2016 that one quarter of spirometry values were not consistent with COPD. Our objective was to explore this further, using patient-anonymised data in Hampshire Health Record Analytical database, an NHS database for ≥1.4 million patients, to compare characteristics, comorbidities and respiratory medication in patients diagnosed with COPD with and without evidence of AFO. Methods Read codes in primary care records were used to identify a prevalent COPD cohort as at 01/01/2011 and define and describe three patient categories based on consistency of FEV1/FVC% since diagnosis: all <70% (persistent AFO), some <70% (variable AFO), all ≥70% (absent AFO). Results 16 479 patients were identified with diagnosed COPD of whom 13 653 (82.9%) had FEV1/FVC% data: 7609 (55.7%) showed persistent AFO, 4413 (32.3%) variable AFO and 1631 (11.9%) absent AFO (Table 1). In the 2826 patients without recorded FEV1/FVC%, half had no evidence of any spirometry. In patients without AFO, mean FEV1/FVC% was high (80.5%), though mean FEV1 was <80% predicted (77.6%). There was no clinically relevant age difference across the groups, but patients without AFO were more often women, had higher mean BMI and contained proportionally fewer active smokers than those with persistent AFO. Never smokers were rare in all groups. Mean number of comorbidities was highest in patients without AFO. Overall, 47.7% of this cohort also had a recorded diagnosis of asthma, slightly more among those with variable AFO unsurprisingly, but with very similar proportions in those with persistent and absent AFO. Among patients without AFO, 58% were receiving some form of respiratory medication (compared to 70% of those with persistent AFO). Many were receiving expensive treatments only recommended for confirmed moderate or severe COPD (long-acting bronchodilators or inhaled corticosteroids). Conclusion Twelve percent of patients with a primary care COPD diagnosis did not have obstructive spirometry. If COPD diagnosis is incorrect, there is potential overuse of harmful or ineffective treatments and other causes of patients’ symptoms may be missed. Abstract P31 Table 1 Baseline demographic and clinical characteristics by consistency of airflow obstruction Consistency of airflow obstruction in patients with FEV1/FVC% (n=13653, 82.9% of total cohort) Persistent (all values FEV1/FVC% <70%) (n=7609, 55.7%) Variable (some values FEV1/FVC% <70%) (n=4413, 32.3%) Absent (all values FEV1/FVC% ≥70%) (n=1631, 11.9%) p-value* Gender male n (%) 4400 (57.8) 2254 (51.1) 752 (46.1) <0.001 Age, years Mean (SD) 69.9 (10.5) 70.8 (10.4) 68.4 (11.7) <0.001 BMI, kg/m2 mean (SD) 26.3 (5.7) 28.1 (5.9) 29.2 (6.7) <0.001 Smoking status n (%) <0.001 Active smoker 2971 (41.0) 1490 (34.5) 534 (35.4) Ex-smoker 4187 (57.7) 2742 (63.5) 915 (60.7) Never smoker 94 (1.3) 83 (1.9) 58 (3.8) FEV1%predicted mean (SD) 54.4 (18.1) 65.2 (18.5) 77.6 (19.3) <0.001 FEV1/FVC% mean (SD) 51.1 (10.6) 66.0 (12.5) 80.5 (7.7) <0.001 MRC Dyspnoea score (1–5) median (IQR) 2 (2,3) 2 (2,3) 2 (1,3) <0.001 Number of comorbidities mean (SD) 2.4 (1.7) 2.9 (1.8) 3.0 (1.9) <0.001 On treatment at baseline n (%) Short-acting bronchodilator 4231 (55.6) 2370 (53.7) 695 (42.6) <0.001 Long-acting bronchodilator 4172 (54.8) 2238 (50.7) 611 (37.5) <0.001 Theophyllines 364 (4.8) 159 (3.6) 36 (2.2) <0.001 Inhaled corticosteroids 3731 (49.0) 2130 (48.3) 631 (38.7) <0.001 Mucolytics 436 (5.7) 205 (4.6) 56 (3.4) <0.001 On none of the above drugs 2266 (29.8) 1283 (29.1) 692 (42.4) <0.001 BMI, body mass index; FEV1, forced expiratory volume in 1 second; FVC, forced vital capacity; MRC, Medical Research Council. *Test for difference depends on variable type / summary measures stated: ANOVA (for mean, SD), Kruskal-Wallis (for median, IQR) and Chi-squared test (for n, %).

S67 Mortality in copd patients following community acquired pneumonia: a population database analysis of linked healthcare records

Introduction Community acquired pneumonia (CAP) is a common occurrence in patients with chronic obstructive pulmonary disease (COPD), yet controversy still remains about its affect on outcome. We therefore investigated the impact of CAP on mortality in a cohort of COPD patients identified from the Hampshire Health Record analytical database, a local NHS database containing linked, anonymised primary and secondary care records. Methods Patients were defined as having COPD if they had a diagnostic Read code in their primary care record at any time prior to the 1st January 2010 and were aged ≥40 years at the start of the study. CAP episodes occurring over a 5-year period from 1st January 2010 were identified using Read and ICD-10 codes. The outcome measure was all-cause mortality following a CAP diagnosis. Cox proportional hazard modelling was used to estimate hazard ratios (HR) and confidence intervals (CI), adjusting for age, sex, GOLD stage, smoking status and inhaled corticosteroid use (ICS)). Results The cohort comprised 14506 COPD patients. The mean age was 70.3 (±10.8) years and 53.6% were male. 1931 (13.3%) patients had at least one CAP and 2870 (19.8%) deaths occurred over the study period. 28.2% of patients diagnosed with CAP died compared to only 9.7% of those without a CAP diagnosis (p < 0.001). Logistic regression analysis, controlling for potential confounders identified CAP as an independent risk factor for future mortality (odds ratio 2.72; CI 2.37–3.12, p < 0.001). Compared to younger individuals (40–59 years) those aged 60–79 and >80 years had the highest mortality risk following CAP (HR 2.65; CI 1.61–4.34, HR 7.03; CI 4.27–11.57 respectively, both p < 0.001). Concurrent use of inhaled Fluticasone or Budesonide were associated with reduced mortality risk following CAP (HR 0.82; CI: 0.68–0.98 p = 0.029, HR 0.55; CI: 0.39–0.76 p < 0.001, respectively) (Figure 1). Conclusion CAP in COPD is associated with increased risk of mortality, especially in older individuals. Although known to increase CAP risk, ICS use appears to reduce risk of mortality following CAP. Further research to understand the mechanisms underlying CAP risk in COPD and modulating effects of ICS is key, to guide development of future, targeted preventative strategies. Abstract S67 Figure 1 Survival comparisons following CAP in COPD patients, stratified by Fluticasone (A) or Budesonide (B) use

P53 Predicting poor outcomes in COPD patients deemed ‘low risk’ by dose score

Introduction COPD continues to cause a substantial symptom, mortality and financial burden in the UK. Current treatment strategies are predominantly reactive as insufficient evidence exists to successfully target clinical resource into pre-emptive ‘early interventions’. The DOSE (dyspnoea, obstruction, smoking status and exacerbation) score has been validated as a risk predictor for mortality, hospitalisation and poorer health status. However, only a small proportion of COPD patients with poor outcomes have high DOSE scores. We sought to establish if clinical characteristics can be used to pre-emptively identify those COPD patients vulnerable to future poor health status by using an electronic database of anonymised patient records-the Hampshire Health Record Analytical Database (HHRA). Methods Within our HHRA database COPD cohort, we identified a cohort of 6890 patients who fell into the ‘low risk’ category by DOSE score (<4). Within this group, a subset met the criteria for poor COPD outcomes over the next four years, defined as; death (all cause), COPD related hospital admission, a DOSE score increase of ≥2 points or a subsequent DOSE score of ≥4 (high risk). We used logistic regression analysis to examine the association between demographic and clinical characteristics documented by Read code at baseline and those who subsequently fell into the poor outcomes subgroup. Results In our ‘low risk’ cohort of 6890 COPD patients, 5000 held sufficient data to be included in the analysis. After four years, 2211 (44.2%) of those 5000 patients fell into the poor outcomes subgroup. As shown in Table 1, poor future outcomes were significantly associated with age, high deprivation decile, low BMI, certain comorbidities, a raised eosinophil percentage (≥2%) and the prescription (in the preceding twelve months) of nebulised bronchodilators, inhaled bronchodilators and an ICS/LABA combination inhaler. A BMI of >25 and rhinosinusitis were associated with a lower risk of poor future outcomes. Conclusions Poor future clinical outcomes appear to be associated with certain clinical characteristics in a COPD database cohort deemed low risk by DOSE score. These findings warrant further validation in a clinical cohort and investigation into the effect of pre-emptive optimisation of these characteristics on health outcomes. Abstract P53 Table 1 Associations between clinical characteristics and odds of future poor clinical outcome *Variables excluded from model due to statistical insignificance: gender, IHD, hypertension, osteoporosis, GORD, diabetes, total number of comotbities. **Decile 10 represents least deprived.