Incidence of depression and antidepressant prescription in patients with COPD: A large UK population-based cohort study.

BACKGROUND: Depression is frequently reported in patients with Chronic Obstructive Pulmonary Disease (COPD). However, there is little information available on the incidence of depression following a COPD diagnosis. OBJECTIVE: To determine the incidence of a new diagnosis of depression or antidepressant prescription in people with and without a COPD diagnosis. METHODS: A matched cohort study was conducted using The Health Improvement Network database. Patients with confirmed COPD diagnosis were matched to up to four subjects without a COPD diagnosis by age, sex and GP practice. Cox proportional hazards models were used to assess the incidence rates of depression and antidepressant prescription. RESULTS: 44,362 patients with COPD and 124,140 subjects without COPD were included. The incidence rate of depression per 1000 person-years following COPD diagnosis was greater (11.4; 95% CI: 10.9-11.8) compared to subjects without COPD (5.7; 95% CI: 5.5-5.8) (p < 0.001). Patients with COPD were 42% more likely to have an incident depression (adjusted hazard ratio [aHR]: 1.42; 95% CI: 1.32-1.53; p < 0.001), and 40% more likely to be prescribed an antidepressant (aHR: 1.40; 95% CI: 1.35-1.45; p < 0.001). The incidence to either depression or antidepressant prescription was also greater for patients with COPD (aHR: 1.41; 95% CI: 1.36-1.46; p < 0.001). Patients with COPD and worse breathlessness had a higher risk of incident depression compared to patients with less breathlessness. CONCLUSION: Healthcare providers managing patients with COPD should be alert to the existence of depression and aware of its symptoms and consequences.

Risk of subtrochanteric and femoral shaft fractures due to bisphosphonate therapy in asthma: a population-based nested case-control study.

Concerns have been raised over the association between bisphosphonates and atypical fractures in subtrochanteric and femoral shaft regions, but the potential risk of these fractures due to bisphosphonate use in asthma has not been examined. INTRODUCTION: Bisphosphonates are used as first-line treatment for osteoporosis; however, concerns have been raised over their association with atypical subtrochanteric (ST) and femoral shaft (FS) fractures. The potential risk of atypical ST/FS fractures from bisphosphonate use in asthma has not been examined. METHODS: A nested case-control study was conducted using linked data from the Clinical Practice Research Datalink (CPRD) and Hospital Episode Statistics (HES) databases. Using an asthma cohort, we identified patients with atypical ST/FS fractures and sex, age, and practice-matched controls. Conditional logistic regression was used to determine the association between bisphosphonate exposure and atypical ST/FS fractures. RESULTS: From a cohort of 69,074 people with asthma, 67 patients with atypical ST/FS fractures and 260 matched control subjects were identified. Of the case patients, 40.3% had received bisphosphonates as compared with 14.2% of the controls corresponding to an adjusted odds ratio (aOR) of 4.42 (95%CI, 2.98 to 8.53). The duration of use influenced the risk with long-term users to be at a greater risk (> 5 years vs no exposure; aOR = 7.67; 95%CI, 1.75 to 33.91). Drug withdrawal was associated with diminished odds of atypical ST/FS fractures. CONCLUSION: Regular review of bisphosphonates should occur in patients with asthma. The risks and benefits of bisphosphonate therapy should be carefully considered in consultation with the patient. To improve AFF prevention, early signs which may warrant imaging, such as prodromal thigh pain, should be discussed.

Risk of incident dementia and cognitive impairment in patients with chronic obstructive pulmonary disease (COPD): A large UK population-based study.

BACKGROUND: Although cognitive impairment and dementia are common comorbidities in patients with chronic obstructive pulmonary disease (COPD), estimates of incidence following a diagnosis of COPD are inconclusive. OBJECTIVE: To determine the incidence of cognitive impairment and dementia in people with and without a COPD diagnosis. METHODS: A population-based study using UK General Practice (GP) health records from The Health Improvement Network database was conducted. Patients with confirmed COPD diagnosis, ≥40 years old, were matched to up to four subjects without a COPD diagnosis by age, sex and GP practice. Cox proportional hazards models were used to assess the incidence rates of cognitive impairment and dementia. RESULTS: Of patients with COPD (n = 62,148), 9% developed cognitive impairment, compared with 7% of subjects without COPD (n = 230,076), p < 0.001. The incidence of cognitive impairment following COPD diagnosis was greater than in subjects without COPD following index date (adjusted Hazard Ratio (aHR), 1.21; 95% CI: 1.16 ─ 1.26, p < 0.001). The coded incidence of either cognitive impairment or dementia was also greater in patients with COPD following adjustment for confounders (aHR: 1.13, 95% CI: 1.09 ─ 1.18, p < 0.001). Coded incident dementia alone was not different between patients with COPD and subjects without COPD (aHR, 0.91, 95% CI: 0.83 ─ 1.01, p = 0.053). CONCLUSION: Despite the increased incidence of cognitive impairment in patients with COPD, incidence of dementia was not as frequently recorded in patients with COPD. This raises the concern of undiagnosed dementia and emphasises the need for a systematic assessment in this population.

Variation in clinical outcomes and process of care measures in community acquired pneumonia: a systematic review.

BACKGROUND: Variation in outcomes of patients with community acquired pneumonia (CAP) has been reported in some, but not all, studies. Although some variation is expected, unwarranted variation in healthcare impacts patient outcomes and equity of care. The aim of this systematic review was to: i) summarise current evidence on regional and inter-hospital variation in the clinical outcomes and process of care measures of patients hospitalised with CAP and ii) assess the strength of this evidence. METHODS: Databases were systematically searched from inception to February 2018 for relevant studies and data independently extracted by two investigators in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. Included studies enrolled adults hospitalised with CAP and reported a measure of variation between two or more units in healthcare outcomes or process of care measures. Outcomes of interest were mortality, length of hospital stay (LOS) and re-admission rates. A structured synthesis of the studies was performed. RESULTS: Twenty-two studies were included in the analysis. The median number of units compared across studies was five (IQR 4-15). Evidence for variation in mortality between units was inconsistent; of eleven studies that performed statistical significance testing, five found significant variation. For LOS, of nine relevant studies, all found statistically significant variation. Four studies reported site of admission accounted for 1-24% of the total observed variation in LOS. A shorter LOS was not associated with increased mortality or readmission rates. For readmission, evidence was mixed; of seven studies, 4 found statistically significant variation. There was consistent evidence for variation in the use of intensive care, obtaining blood cultures on admission, receiving antibiotics within 8 h of admission and duration of intravenous antibiotics. Across all outcome measures, only one study accounted for natural variation between units in their analysis. CONCLUSION: There is consistent evidence of moderate quality for significant variation in length of stay and process of care measures but not for in-patient mortality or hospital re-admission. Evidence linking variation in outcomes with variation in process of care measures was limited; where present no difference in mortality was detected despite POC variation. Adjustment for natural variation within studies was lacking; the proportion of observed variation due to chance is not quantified by existing evidence.

Spinal or general anaesthesia for surgical repair of hip fracture and subsequent risk of mortality and morbidity: a database analysis using propensity score-matching.

Around 76,000 people fracture their hip annually in the UK at a considerable personal, social and financial cost. Despite longstanding debate, the optimal mode of anaesthesia (general or spinal) remains unclear. Our aim was to assess whether there is a significant difference in mortality and morbidity between patients undergoing spinal anaesthesia compared with general anaesthesia during hip fracture surgery. A secondary analysis examined whether a difference exists in mortality for patients with pre-existing cardiovascular disease or chronic obstructive pulmonary disease. This was a clinical database analysis of patients treated for hip fracture in Nottingham, UK between 2004 and 2015. Propensity score-matching was used to generate matched pairs of patients, one of whom underwent each mode of anaesthesia. Data were analysed using conditional logistic regression, with 7164 patients successfully matched. There was no difference in 30- or 90-day mortality in patients who had spinal rather than general anaesthesia (OR [95%CI] 0.97 [0.8-1.15]; p = 0.764 and 0.93 [0.82-1.05]; p = 0.247 respectively). Patients who had a spinal anaesthetic had a lower-risk of blood transfusion (OR [95%CI] 0.84 [0.75-0.94]; p = 0.003) and urinary tract infection (OR [95%CI] 0.72 [0.61-0.84]; p < 0.001), but were more likely to develop a chest infection (OR [95%CI] 1.23 [1.07-1.42]; p = 0.004), deep vein thrombosis (OR [95%CI] 2.18 [1.07-4.45]; p = 0.032) or pulmonary embolism (OR [95%CI] 2.23 [1.16-4.29]; p = 0.016). The mode of anaesthesia for hip fracture surgery resulted in no significant difference in mortality, but there was a significant difference in several measures of postoperative morbidity.

The utility of exhaled nitric oxide in patients with suspected asthma.

The value of FENO measurements in patients with symptoms suggestive of asthma is unclear. We performed an observational study to assess the ability of FENO to diagnose asthma and to predict response to inhaled corticosteroids (ICS). Our findings suggest FENO is not useful for asthma diagnosis but is accurate at predicting ICS response.

The UK prevalence of hereditary haemorrhagic telangiectasia and its association with sex, socioeconomic status and region of residence: a population-based study.

BACKGROUND: Hereditary haemorrhagic telangiectasia (HHT) is an autosomal dominant genetic disorder of aberrant blood vessel development characterised by arteriovenous malformations. HHT is associated with significant morbidity due to complications including epistaxis, gastrointestinal bleeding and stroke. We explored the hypothesis that a diagnosis of HHT is associated with sex, socioeconomic status and geographical location. METHODS: We used The Health Improvement Network, a longitudinal, computerised general practice database covering 5% of the UK population to calculate prevalence estimates for HHT stratified by age, sex, socioeconomic status and geographical location. RESULTS: The 2010 UK point prevalence for HHT was 1.06/10 000 person years (95% CI 0.95 to 1.17) or 1 in 9400 individuals. The diagnosed prevalence of HHT was significantly higher in women compared with men (adjusted prevalence rate ratio (PRR) 1.53, 95% CI 1.24 to 1.88) and in those from the most affluent socioeconomic group compared with the least (adjusted PRR 1.74, 95% CI 1.14 to 2.64). The PRR varied between different regions of the UK, being highest in the South West and lowest in the West Midlands (adjusted PRR for former compared with latter 1.86, 95% CI 1.61 to 2.15). CONCLUSIONS: HHT prevalence is more common in the UK population than previously demonstrated, though this updated figure is still likely to be an underestimate. HHT appears to be significantly under-diagnosed in men, which is likely to reflect their lower rates of consultation with primary care services. There is under-diagnosis in patients from lower socioeconomic groups and a marked variation in the prevalence of diagnosis between different geographical regions across the UK that requires further investigation.

Does early life exposure to antibiotics increase the risk of eczema? A systematic review.

A number of studies have suggested that early life exposure to antibiotics can lead to an increased risk of developing eczema. This systematic review and meta-analysis of observational studies, involving children or young adults aged 0-25 years, assessed the impact of antibiotic exposure either in utero or during the first 12 months of life on subsequent eczema risk. Twenty studies examined the association between prenatal and/or postnatal exposure to antibiotics and development of eczema. The pooled odds ratio (OR) for the 17 studies examining postnatal antibiotic exposure was 1.41 [95% confidence interval (CI) 1.30-1.53]. The pooled OR for the 10 longitudinal studies was 1.40 (95% CI 1.19-1.64), compared with a pooled OR of 1.43 (95% CI 1.36-1.51) for the seven cross-sectional studies. There was a significant dose-response association, suggesting a 7% increase in the risk of eczema for each additional antibiotic course received during the first year of life [pooled OR 1.07 (95% CI 1.02-1.11)]. Finally, the pooled OR for the four studies relating to antenatal exposure was 1.30 (95% CI 0.86-1.95). We conclude that exposure to antibiotics in the first year of life, but not prenatally, is more common in children with eczema.

The incidence of pneumonia using data from a computerized general practice database.

Despite being widely recognized as a significant public health problem there are surprisingly few contemporary data available on the incidence of pneumonia in the UK. We conducted a general population-based cohort study to determine the incidence of pneumonia in general practice in the United Kingdom. Data were obtained from The Health Improvement Network (THIN) - a computerized, longitudinal, general practice database. Recorded diagnoses of pneumonia between 1991 and 2003 were used to calculate the incidence of pneumonia stratified by year, sex, age group and deprivation score. The overall incidence of pneumonia was 233/100 000 person-years [95% confidence interval (CI) 231-235] and this rate was stable between 1991 and 2003. The incidence of pneumonia was slightly lower in females compared to males [age-adjusted incidence rate ratio (IRR) 0.88, 95% CI 0.86-0.89]. Pneumonia was most common in children aged <4 years and adults aged >65 years. There was an increased incidence of pneumonia with higher levels of socioeconomic disadvantage such that people living in the most deprived areas of the United Kingdom were 28% more likely to get pneumonia than those in the least deprived areas (age- and gender-adjusted IRR 1.28, 95% CI 1.24-1.32). In conclusion, pneumonia is an important public health problem and the incidence of pneumonia is higher in people at the extremes of age, men and people living in socially deprived areas.

Effect of maternal asthma, exacerbations and asthma medication use on congenital malformations in offspring: a UK population-based study.

BACKGROUND: Clinical advice to pregnant women with asthma is to maintain optimal therapeutic management; however, potential adverse effects of asthma treatments on fetal development remain uncertain. A study was undertaken to assess the association between maternal asthma and gestational exposure to asthma medications with risk of congenital malformation in offspring. METHODS: A matched case-control study was performed using The Health Improvement Network primary care database. Children with malformations were matched to control children on birth year, general practice and singleton or twin delivery. RESULTS: 5124 cases of liveborn children with major congenital malformations and 30,053 controls were included in the study. The risk of any malformation in children born to women with asthma was marginally higher than that in children born to women without asthma (adjusted OR 1.10, 95% CI 1.01 to 1.20). However, no association was present in children born to mothers receiving asthma treatment in the year before or during pregnancy (OR 1.06, 95% CI 0.94 to 1.20). In assessing teratogenicity of medications, no increased risk of malformation was found with gestational exposures to short- or long-acting beta agonists, inhaled corticosteroids, oral corticosteroids, other bronchodilators or cromones. These findings were similar for each of 11 system-specific malformation groups, except for an increase in musculo-skeletal system malformation associated with cromone exposure. CONCLUSIONS: Gestational exposure to commonly used asthma medications was found to be safe overall, although a moderate teratogenic risk of cromones cannot be excluded. There was some evidence of a small increased risk of congenital malformation in children born to women with asthma, but this was not explained by gestational exposure to asthma drugs.

The association between serum osmolality and lung function among adults.

The extensive pulmonary vasculature results in the lungs being intimately exposed to circulating blood. As increased serum osmolality may be associated with an increase in pro-inflammatory activity, this has the potential to result in damage to the lungs and reduced lung function. The objective of the present study was to test the hypothesis that increased serum osmolality is associated with a lower forced expiratory volume in one second (FEV(1)) and forced vital capacity (FVC). The present study was a cross-sectional study of 10,602 participants in the Third National Health and Nutrition Examination Survey aged > or = 17 yrs for whom there were adequate data on all outcomes and exposures. After adjustment for age, smoking and other confounding factors, increased serum osmolality was inversely associated with both FEV(1) and FVC. An increase of 1 sd in serum osmolality was associated with a decrease in both FEV(1) of 19.8 mL and FVC of 35.3 mL. The constituent assays demonstrated a complex relationship with both FEV(1) and FVC. Increased serum osmolality was associated with decreased forced expiratory volume in one second and forced vital capacity. If causal, this may have implications for the understanding of the processes that are involved in the pathophysiology of decline in lung function.

The relation between dietary intake of individual fatty acids, FEV1 and respiratory disease in Dutch adults.

BACKGROUND: A reduced dietary intake of n-3 fatty acids, in association with increased n-6 fatty acid intake, has been proposed as a potential aetiological factor for chronic obstructive pulmonary disease (COPD) and asthma. However, the relative importance of individual fatty acids within the n-3 and n-6 categories on this effect has not been widely investigated. We have studied the relation between individual fatty acid intakes, lung function and self-reported respiratory symptoms and diagnoses in a representative sample of more than 13,000 Dutch adults. METHODS: Intake of individual fatty acids was estimated by a food frequency questionnaire and analysed in relation to measures of forced expiratory volume in 1 s (FEV1) and to questionnaire reported wheeze, asthma and COPD symptoms. RESULTS: After adjusting for confounding, we found no protective association between individual n-3 fatty acid intakes and FEV1. Higher intakes of some n-6 fatty acids were associated with lower FEV1, this effect being most marked for c22:4 n-6 docosatetraenoic acid (reduction in FEV1 between the highest and lowest quintile of intake 54.5 ml (95% CI -81.6 to -27.4)). Most of the n-6 fatty acid effects interacted significantly with smoking, their effects being strongest in current smokers. Individual n-3 fatty acid intakes were generally associated with a higher risk of wheeze in the past year, but otherwise there was little or no association between fatty acid intake and wheeze, doctor diagnosed asthma or other respiratory symptoms. CONCLUSIONS: A high intake of n-3 fatty acids does not appear to protect against COPD or asthma, but a high intake of several n-6 fatty acids is associated with a significant reduction in FEV1, particularly in smokers. These findings indicate that high dietary intake of n-6 fatty acids, rather than reduced n-3 intake, may have an adverse effect on lung health.

Fertility rates in women with asthma, eczema, and hay fever: a general population-based cohort study.

The protective association between having older siblings and the risk of subsequent allergic disease may be due to decreased fertility among women with allergic disease. In this study, the authors compared fertility rates among women with asthma, eczema, or hay fever with those in the general female population. Computerized primary-care data from the United Kingdom were used to conduct a cohort analysis of 491,516 women. General fertility rates and age-specific fertility rates for 1994-2004 were estimated. Using Poisson regression, the authors compared fertility rates among women with asthma, eczema, or hay fever with rates in women without these diagnoses. Fertility rates were 53.0 and 52.3 livebirths per 1,000 person-years in women with and without asthma, respectively. The fertility rate ratio for women with asthma compared with women without asthma was 1.02 (95% confidence interval (CI): 1.00, 1.04) after adjustment for age, smoking, body mass index, and socioeconomic status. Equivalent fertility rate ratios for eczema and hay fever were 1.15 (95% CI: 1.13, 1.17) and 1.08 (95% CI: 1.06, 1.10), respectively. The authors found no evidence that the fertility rates of women with asthma, eczema, or hay fever are lower than those of women in the general population.

Trends in survival from muscular dystrophy in England and Wales and impact on respiratory services.

Respiratory failure is an important terminal event in muscular dystrophy, but increasingly is effectively treated by non-invasive ventilation. This study was designed to assess mortality statistics in this patient group in order to get an indication of future demand. Mortality data for all deaths from muscular dystrophy registered by death certification in England and Wales between 1993 and 1999 were analysed. In total, 817 deaths from muscular dystrophy were registered between 1993 and 1999. Annual number of deaths was unchanged over this period. Median age at death (interquartile range) for all cause muscular dystrophy increased from 20 (17-42.5) years in 1993, to 26 (17.5-63) years in 1999. Respiratory failure was the primary or contributory cause of death in 82% of cases. Two thirds of these deaths were during acute infection. We can expect 100 patients with muscular dystrophy to develop respiratory failure in England and Wales each year, so non-invasive ventilation services probably need to be able to provide for 0.2 new patients per 100,000 population annually. Respiratory services also need to provide adequate monitoring and early treatment of infection in these patients.

A case-control study of dietary and erythrocyte membrane fatty acids in asthma.

BACKGROUND: Epidemiological evidence suggests that increased dietary omega-6 and reduced omega-3 fatty acid intake, may have contributed to the rising prevalence of asthma, but these hypotheses have not been tested in studies comparing both dietary intake and objective measures of polyunsaturated fatty acids. OBJECTIVE: To assess whether a higher intake of omega-6 or a lower intake of omega-3 fatty acids increases the risk of asthma, by measuring dietary fatty acid intake by a food frequency questionnaire (FFQ) and erythrocyte membrane fatty acids, as an objective biomarker of intake. METHODS: We have compared individual fatty acid intake estimated by FFQ and by mass spectrometry of fasting erythrocyte cell membranes in 89 cases of asthma and 89 community-matched controls. RESULTS: The odds of asthma were increased in relation to intake of the omega-3 fatty acids eicosapentaenoic acid (odds ratio (OR) for difference between the 25th and 75th centiles of intake= 1.89, 95% CI 1.15-3.11) and docosahexaenoic acid (OR = 2.11, 95% CI 1.19-3.74). There was no evidence of any difference in erythrocyte membrane levels of omega-3 fatty acids, while the odds of asthma were reduced in relation to linoleic acid (omega-6) membrane levels (OR = 0.45, 95% CI 0.21-0.95). CONCLUSION: These findings suggest that dietary omega-3 fatty acids do not play a major role in protecting against asthma, and that higher levels of erythrocyte membrane linoleic acid are associated with a lower risk of asthma.

Respiratory symptoms in patients with treated hypothyroidism and inflammatory bowel disease.

BACKGROUND: Patients with idiopathic chronic cough and unexplained airflow obstruction in non-smokers have been shown to have an increased prevalence of hypothyroidism and other organ specific autoimmune disorders. Whether patients with hypothyroidism have an increased prevalence of respiratory symptoms is unknown. METHODS: The prevalence of respiratory symptoms was assessed in 124 patients with treated hypothyroidism recruited from primary and secondary care, 64 outpatients with inflammatory bowel disease, and 1346 control adults recruited randomly from the electoral register in a case-control study. Respiratory symptoms and smoking history were assessed by a respiratory symptom questionnaire. RESULTS: After adjustment for age, sex and smoking, symptoms of breathlessness and sputum production were more prevalent in both patient populations than in controls (odds ratios for hypothyroidism and inflammatory bowel disease; breathlessness: 3.1 (95% CI 2.1 to 4.6) and 3.4 (95% CI 2.0 to 6.0), respectively; sputum production: 2.7 (95% CI 1.6 to 4.5) and 2.5 (95% CI 1.2 to 5.0), respectively). Cough during the day and night was significantly more prevalent in patients with hypothyroidism (1.8 (95% CI 1.2 to 2.9)) and approached significance in those with inflammatory bowel disease (1.8 (95% CI 1.0 to 3.4)). Wheeze and nocturnal cough were no more prevalent in either disease population than in controls. CONCLUSION: There is a significantly increased prevalence of respiratory symptoms in patients with hypothyroidism or inflammatory bowel disease compared with controls recruited from the general population. Further work is required to determine whether similar differences are seen in comparison with hospital based controls. These findings support the hypothesis that there is a link between autoimmune hypothyroidism and respiratory disease.

Siblings, multiple births, and the incidence of allergic disease: a birth cohort study using the West Midlands general practice research database.

BACKGROUND: The presence of older siblings reduces the risk of developing hay fever, eczema and atopy, but findings for asthma have been inconsistent. Whether twins have a reduced risk of allergic disease is also unclear. We have investigated these questions in a birth cohort analysis of the West Midlands General Practice Research Database (GPRD). METHODS: Our birth cohort included 29,238 children. The incidence of allergic disease was examined according to the number of siblings, multiple births, and parental allergic disease and smoking habit using Cox regression. RESULTS: There was a dose related decrease in the incidence of eczema and hay fever with increasing number of older siblings (hazard ratio for children with three or more older siblings compared with none 0.70 (95% CI 0.64 to 0.76) for eczema and 0.67 (95% CI 0.52 to 0.86) for hay fever). In contrast, the presence of older siblings increased the incidence of asthma (HR 1.17, 95% CI 1.06 to 1.29), although this effect was strongly dependent on age of diagnosis. For children diagnosed over the age of 2 years the presence of older siblings was protective (HR 0.66, 95% CI 0.52 to 0.82), while below this age the reverse was true (HR 1.38, 95% CI 1.24 to 1.54). Members of a multiple birth had a reduced incidence of all three allergic diseases. Birth order and multiple birth effects were independent of sex, maternal age, consulting behaviour, and parental allergy and smoking habit. CONCLUSIONS: The presence of older siblings and being a member of a multiple birth appears to protect against the development of eczema, hay fever, and asthma diagnosed after the age of 2. In contrast, the presence of older siblings increases the incidence of early asthma.