Asthma

Reduced lung function in neonates is associated with an increased risk of asthma at age 7

Bisgaard et al. Interaction between asthma and lung function growth in early life.

Am J Resp Crit Care Med 2012;185:1183–9

http://dx.doi.org/10.1164/rccm.201110-1922OC

The Copenhagen Prospective Study on Asthma in Childhood is a prospective cohort study of 411 children considered ‘at-risk’ for asthma set up to analyse the interaction between lung function development and asthma from birth through to the age of 7. What's really impressive is that spirometry and bronchial methacholine responsiveness were performed in 403/411 neonates (98%) using forced flow-volume measurements whilst they were under sedation. Spirometry was then repeated in 317 of the 403 children (77%) 7 years later. Asthma was diagnosed prospectively from daily diary cards and clinic visits every 6 months. Children with asthma at age 7 (14%) already had significant airflow deficit as neonates (forced expiratory flow at 50% of vital capacity reduced by 0.34 z score by 1 month of age [P = 0.03]) and this deficit progressed until the age of 7. In fact, approximately 40% of the airflow deficit associated with asthma was present at birth and 60% developed later with the disease. Neonatal bronchial responsiveness to methacholine was also associated with the development of asthma [P = 0.01]. Further research into the origins of asthma will therefore need to focus on antenatal, perinatal and neonatal factors.

Children with asthma more likely to get H1N1 influenza

Kloepfer et al. Increased H1N1 infection rate in children with asthma.

Am J Resp Crit Care Med 2012;185:1275–9

http://dx.doi.org/10.1164/rccm.201109-1635OC

This US study evaluated 161 children (95 with asthma, 66 without) aged 4–12 years to assess whether children with asthma had a higher H1N1 infectivity rate and illness severity during the peak 2009 H1N1 flu season. The children were able to provide at least 6 out of 8 weekly nasal mucus samples which were then analysed for viral aetiology. The incidence of H1N1 infection was significantly higher in children with asthma than those without [41% versus 24%; odds ratio (OR) 4.0; 95% CI 1.8 — 9.0]. Rates of rhinovirus and other viral infections were similar [47% vs 41%]. For the children with asthma, there was a highly suggestive but non-significant trend to loss of asthma control during H1N1 infection compared with rhinovirus infection [38% vs 21%; OR 2.6; 95% CI 0.9 — 7.2]. Given the increased susceptibility of children with asthma to H1N1 infection, the authors emphasise the need for yearly influenza vaccination in children. New research now needs to focus on the way(s) in which asthma enhances susceptibility to H1N1 influenza infection…

No adverse side-effects from maternal use of folic acid supplements in pregnancy on childhood wheeze and asthma

Bekkers et al. Maternal use of folic acid supplements during pregnancy, and childhood respiratory health and atopy.

Eur Respir J 2012;39:1468–74

http://dx.doi.org/10.1183/09031936.00094511

Concerns have been raised previously regarding the use of folic acid supplements during pregnancy and possible adverse side-effects on the foetus such as increased wheeze and asthma in early childhood. This study from the Netherlands generally puts those fears to rest. Data on maternal use of folic acid supplements were available for 3,786 children entered into the Prevention and Incidence of Asthma and Mite Allergy birth cohort study. Data on the children's respiratory and allergic symptoms were collected annually by questionnaire, and allergic sensitisation and bronchial hyper-responsiveness (BHR) were measured at 8 years of age. Maternal folic acid use was associated with a slightly increased prevalence of wheeze at age 1 [prevalence ratio 1.20; 95% CI 1.04 — 1.39] but not at any other age. Otherwise, there was no association between maternal folic acid use and frequent asthma symptoms, wheeze, respiratory tract infections or eczema. In addition, maternal folic acid use was not associated with sensitisation or BHR. This is certainly reassuring…

Asthma and rhinitis: further evidence for the ‘one airway’ hypothesis…

de Groot et al. Allergic rhinitis is associated with poor asthma control in children with asthma.

Thorax 2012;67:582–7

http://dx.doi.org/10.1136/thoraxjnl-2011-201168

Over 80% of patients with asthma also have rhinitis. Both conditions share similar pathophysiological characteristics, and there is considerable evidence for a link between the two conditions — for a recent summary see http://dx.doi.org/10.4104/pcrj.2012.00035. However, there is still debate on whether asthma control can be improved by treating concomitant rhinitis. This was a cross-sectional survey in 203 children with asthma aged 5–18 years using the ISAAC rhinitis questionnaire and the Asthma Control Questionnaire (ACQ), together with measurement of fraction of exhaled nitric oxide (FeNO) and specific IgE levels. 157 children (76.2%) had allergic rhinitis (AR) symptoms, but only 88 (56.1%) had been diagnosed. Patients with AR were more likely to have an ACQ score ≥ 1 (signifying ‘incomplete’ asthma control) than those without AR [odds ratio (OR) 2.74; 95% CI 1.28 — 5.91] irrespective of FeNO or specific IgE levels. However, after adjustment for nasal inhaled corticosteroid treatment, AR was no longer associated with incomplete asthma control [OR 0.72; 95% CI 0.47 — 1.12]. The authors conclude that AR has a major impact on asthma control independent of lower airway inflammation or aeroallergen sensitisation; furthermore, treating AR with nasal corticosteroids in children seems to improve asthma control — but this now needs to be confirmed with evidence from more definitive RCTs.

Allergy

Oral immunotherapy can treat egg allergy in children

Burks et al. Oral immunotherapy for treatment of egg allergy in children.

New Engl J Med 2012;367:233–43

http://www.nejm.org/doi/full/10.1056/NEJMoa1200435

Food allergies affect up to 8% of children and 2% of adults, and usually occur in individuals with a personal or family history of atopic disorders such as asthma. The mainstay of current treatment is allergen avoidance. However, immunotherapy (controlled exposure to very small but progressively increasing doses of the identified allergen until a maintenance dose is reached) leading to desensitisation has become an established treatment for some types of allergy, and potentially could be used to treat food allergy. A systematic review on the use of oral immunotherapy (OIT) for treating peanut allergy was published recently [see http://dx.doi.org/10.4104/pcrj.2011.00071]. This was a double-blind, randomised controlled trial (RCT) of OIT (n = 40) versus placebo (n = 15) in children with egg allergy aged 5 to 11. Initial OIT treatment was followed by an oral food challenge of egg-white powder at 10 and 22 months. If passed successfully, OIT treatment was discontinued, all egg consumption avoided, and the children were given a further oral food challenge at 24 months. 55% of the OIT group and none of the placebo group passed the 10-month challenge. 75% of the OIT group passed the 22-month challenge, and 28% of these (11/40) passed the 24-month challenge and were able to eat egg a year later. OIT therefore produced high levels of desensitisation, and a significant number of these desensitised children achieved tolerance such that they were able to consume egg a year later. This is a major breakthrough.

COPD

Inflammatory biomarkers may improve prediction of COPD mortality

Celli et al. Inflammatory biomarkers improve clinical prediction of mortality in chronic obstructive pulmonary disease.

Am J Resp Crit Care Med 2012;185:1065–72

http://dx.doi.org/10.1164/rccm.201110-1792OC

Accurately predicting mortality can help us target interventions for patients with COPD. Given that COPD is characterised by low-grade systemic inflammation, can the use of inflammatory biomarkers improve the performance of established predictive factors? 1,843 patients enrolled in the ECLIPSE study (a longitudinal study to identify predictive surrogate endpoints) were followed-up for three years. Analysis of clinical variables included Kaplan-Meier plots, log-rank analysis and Cox proportional hazards, whilst C statistics assessed the predictive power of various biomarkers. Data on patient characteristics, spirometry, 6-minute walking distance, dyspnoea, BODE index, history of hospitalisation, co-morbidities, and CT scan evidence of emphysema were collected. White blood cell counts, fibrinogen and chemokine levels, surfactant protein D, C-reactive protein, Clara cell proteins, IL-6 and −8, and tumour necrosis factor were measured at study visits. Those patients who died (n = 168, 9.1%) were older, had worse airflow obstruction, worse dyspnoea, higher BODE score, more emphysema and higher rates of co-morbidities and hospitalisation. The best predictive model used age, BODE and hospitalisation history [C statistic 0.686; P < 0.001]. Adding information on IL-6 levels improved the C statistic to 0.708, and addition of all biomarkers improved it to 0.726 [P = 0.003]. The effectiveness of this prediction model now needs to be validated in an independent dataset to confirm whether using biomarkers may indeed help improve prediction of mortality in COPD…

An automated telephone system as a tool for assessing COPD exacerbation rates

Bischoff et al. Validity of an automated telephonic system to assess COPD exacerbation rates.

Eur Respir J 2012;39:1090–6

http://dx.doi.org/10.1183/09031936.00057811

This study has important implications for COPD researchers. The authors assessed the validity of an automated telephone exacerbation assessment system (TEXAS) and compared it with existing tools for detecting and recording COPD exacerbations. Over a 1-year period, 86 patients (22.1% female, mean age 66.5 years, mean FEV1 53.4% predicted) were called once every two weeks by TEXAS to record changes in respiratory symptoms, unscheduled healthcare utilisation and use of medication. These patient responses were verified by trained research assistants who performed home visits to collect exacerbation-related information; importantly, they didn't provide any patient care. Commonly-used definitions of exacerbations applied. Detection rates, compliance and patient preference were assessed and compared with paper diary cards and medical record review. 1,824 telephone calls were recorded; 292 were verified by home visits (median four calls per patient; IQR three to five). The validity of the TEXAS system was high, with sensitivities of 66% and specificities of 98%. Exacerbation detection rates and patient compliance differed extensively between the different tools, but were highest with TEXAS. Therefore, TEXAS performed well. However, different tools record different COPD exacerbation rates, making it almost impossible to compare exacerbation rates in different studies unless the same tool has been used…

Prevalence of COPD in non-smokers

Hagstad et al. COPD among non-smokers — report from the Obstructive Lung Disease in Northern Sweden (OLIN) studies.

Resp Med 2012;106:980–8

http://dx.doi.org/10.1016/j.rmed.2012.03.010

In the industrialised world, tobacco smoking is the most important risk factor for COPD. But what about non-smokers? Do they get COPD? These authors from Northern Sweden studied the prevalence of and risk factors for COPD in non-smokers. A random sample of 2470 subjects drawn from a population-based postal survey of 10,040 adults aged 20–77 were invited to structured interviews and lung function testing. 1897 (76.8%) participated. COPD was classified according to both the GOLD fixed FEV1/FVC 0.7 ratio and the lower limit of normal (LLN). In non-smokers, the prevalence of airflow obstruction was 6.9% (3.5% GOLD stage II or above), which was strongly related to increasing age. Of all those with airflow obstruction, 14.1% of men and 26.8% of women were non-smokers. Non-smokers with GOLD stage II or higher airflow obstruction had significantly more symptoms and higher co-morbidity than non-smokers without airflow obstruction. Sex, residential area and exposure to environmental tobacco smoke were not significantly associated with airflow obstruction among non-smokers. Using LLN to define obstruction yielded similar results. Therefore, further research into the reasons for airflow obstruction in non-smokers is required.

Trends in the management of acute myocardial infarction in patients with COPD

Stefan et al. The impact of COPD on management and outcomes of patients hospitalised with acute myocardial infarction: a 10-year retrospective observational study.

Chest 2012;141:1441–8

http://dx.doi.org/10.1378/chest.11-2032

Patients with COPD often have a number of important co-morbidities, and this retrospective observational study from Massachusetts, USA, describes the variation in care received by COPD patients versus non-COPD patients hospitalised with acute myocardial infarction (MI) between 1997 and 2007. Data were obtained on 6,290 patients, 17% of whom had COPD. COPD patients were at higher risk of dying during their hospital stay [13.5% vs 10.1%] and at 30 days post-discharge [18.7% vs 13.2%], and these outcomes remained the same over the 10-year period. After adjustment for multivariable confounders, the adverse effects of having COPD remained for both in-hospital [OR 1.25; 95% CI 0.99 — 1.50] and 30-day [OR 1.31; 95% CI 1.10 — 1.58] all-cause mortality. COPD patients were less likely to be treated with beta-blockers or statins and were less likely to have had interventional treatment for their MI than non-COPD patients, but this gap in care did reduce over the 10-year period. Despite this, COPD patients continue to be less aggressively treated and to have increased adverse outcomes compared with non-COPD patients. A salutary reminder for us all…

Green or yellow sputum colour is a strong predictor of bacterial infection in acute exacerbations of chronic bronchitis

Miravitlles et al. Sputum colour and bacteria in chronic bronchitis exacerbations: a pooled analysis.

Eur Respir J 2012;39:1354–60

http://dx.doi.org/10.1183/09031936.00042111

As part of our routine history-taking when seeing a patient with a productive cough we almost invariably enquire and report the colour of the sputum. But is this relevant, and does it predict the type of infection and/or should it influence prescribing behaviour? These authors pooled data from 6 multicentre studies comparing moxifloxacin with other antibiotics in patients with an acute exacerbation of chronic bronchitis. Sputum samples were taken prior to antibiotic therapy and analysed for microbial aetiology, and the association between sputum colour and bacteria was determined using logistic regression. 4,003 out of 4,089 sputum samples were coloured, and 1,898 (46.6%) were culture positive. Green or yellow sputum was most likely to yield bacteria, and this was the strongest factor predicting a positive culture. Other factors were sputum purulence, increased dyspnoea, male sex, and absence of fever. Having green or yellow versus white sputum had a sensitivity of 94.7% and specificity of 15% for the presence of bacteria. Therefore sputum colour was a stronger predictor of pathogenic bacterial infection than sputum purulence or increased dyspnoea. So we should indeed continue to ask patients about the colour of their sputum…

Treatment of chronic bronchitis exacerbations with moxifloxacin — is as effective as co-amoxiclav

Wilson et al. Moxifloxacin versus amoxicillin/clavulanic acid in outpatient acute exacerbations of COPD: MAESTRAL results.

Eur Respir J 2012;39:1354–60

http://dx.doi.org/10.1183/09031936.00090311

It's good to get evidence-based advice on the choice of antibiotic for treating acute exacerbations of COPD. The Moxifloxacin in Acute ExacerbationS of chronic bronchitis TRiAL (MAESTRAL) was a randomised double-blind non-inferiority (i.e. equivalence) study of moxifloxacin (400 mg four-times daily) versus amoxicillin/clavulanic acid (co-amoxiclav 975/125 mg twice daily) in patients aged ≥ 60 years. Inclusion criteria were Anthonisen type 1 COPD exacerbations (i.e. increased dyspnoea, increased sputum volume and increased sputum purulence), FEV1 < 60% predicted, and 2 or more exacerbations in the previous year. Patients were randomised after stratification by steroid use. The primary end-point was clinical failure (persisting infection after treatment) 8 weeks post-therapy. Overall, moxifloxacin was comparable to co-amoxiclav [111/538 (20.6%) versus 114/518 (22.0%) treatment failures; 95% CI −5.89 — 3.83%]. Patients treated with oral steroids had more severe disease and higher failure rates. In patients with confirmed bacterial exacerbations, moxiflaxicin led to lower treatment failure rates than co-amoxiclav [62/327 (19.0%) vs. 85/335 (25.4%); P = 0.016]. Therefore, moxifloxacin was as effective as co-amoxiclav in the treatment of acute exacerbations of COPD, and both therapies were well tolerated.

The effect of co-morbidities on COPD mortality risk

Divo et al. Comorbidities and risk of mortality in patients with chronic obstructive pulmonary disease.

Am J Resp Crit Care Med 2012;186:155–61

http://dx.doi.org/10.1164/rccm.201201-0034OC

There are a number of multidimensional indices for the assessment of COPD in clinical practice, and the BODE index (Body mass index, airflow Obstruction, Dyspnoea, Exercise capacity), which was first published in 2004, is the best known of these. Here, the BODE Collaborative Group prospectively evaluated 79 co-morbidities recorded in 1,664 COPD patients over 51 months. Using Cox proportional hazard ratios and multivariate analysis, 12/79 co-morbidities were shown to increase the risk of death and were therefore integrated into a COPD-specific co-morbidity test (COTE index).This COTE index was then used to predict mortality risk: increases in the COTE index were associated with an increased risk of death from COPD-related [hazard ratio (HR) 1.13; 95% CI 1.08 — 1.18] and non-COPD-related [HR 1.18; 85% CI 1.15 — 1.21] causes. They then explored whether the COTE index added predictive information when used with the validated BODE index. Increases in both BODE and COTE scores were independently associated with increased risk of death: a COTE score of ≥4 increased by over two-fold the risk of death [HR 2.26 — 2.68; P<0.001] in all BODE quartiles. The authors conclude that this simple disease-specific co-morbidities index (COTE) helps predict mortality risk in COPD patients.

How responsive is the CAT?

Jones et al. Tests of the responsiveness of the COPD Assessment Test following acute exacerbation and pulmonary rehabilitation.

Chest 2012;142:134–40

http://dx.doi.org/10.1378/chest.11-0309

This paper reports two studies on the responsiveness of the 8-item COPD Assessment Test (CAT). The first assessed CAT responsiveness to changes in health status in 67 patients during the first fortnight of an exacerbation; the second assessed CAT responsiveness in 64 patients during days 1–42 of pulmonary rehabilitation (PR). In the first study, mean 14-day improvement in CAT score was −1.4 +/− 5.3 units [P=0.03], but this was −0.2 +/− 5.0 in responders. In study 2, the mean improvement in CAT score following 42 days of PR was −2.2 +/− 5.3 (P=0.002). When compared to more complex COPD health status measures such as the Chronic Respiratory Questionnaire-Self-Administered Standardized (CRQ-SAS), CAT and CRQ-SAS scores correlated at baseline [P<0.0001] and following PR [P<0.01]. Correlations were less strong with the St Georges Respiratory Questionnaire. The authors conclude that the CAT is sensitive to changes in health status following exacerbations, and is as responsive to PR as more complex COPD health status measures. Yet further evidence that the CAT is a useful measurement of COPD health status.

Infections

Community-acquired pneumonia in younger patients aged under 65 is different

Klapdor et al. Community-acquired pneumonia in younger patients is an entity on its own.

Eur Respir J 2012;39:1156–61

http://dx.doi.org/10.1183/09031936.00110911

Though community-acquired pneumonia (CAP) is more common in elderly patients, is CAP in younger patients similar? These authors used data from the prospective multi-centre Competence Network for Community Acquired Pneumonia Study Group (CAPNETZ) database to analyse potential differences in baseline characteristics, co-morbidities, clinical presentation, microbial investigation, aetiology, antimicrobial treatment and outcomes in patients aged 18 — 64 versus those aged 65 and over. 7,803 patients with CAP confirmed by chest X-ray were studied. 52% were aged < 65 years, and co-morbidity was present in only 46.6% (vs. 88.2% in older patients). In younger patients, fever and chest pain were more common, and most had mild CAP with 74.0% having a CURB-65 score of 0 (i.e. no confusion, urea < 7 mM, respiratory rate < 30/min, normal blood pressure, age < 65). Strep. pneumonia and Mycoplasma pneumonia were the most frequent pathogens in younger patients, and short-term and long-term mortality rates were very low (1.7% vs. 8.2% and 0.3% vs. 2.4%, respectively) and even less in patients without co-morbidities. The features of CAP appear to change in the fifth and sixth decades, so CAP in younger patients does indeed look like a clinically distinct entity.

Macrolides improve outcomes in patients with acute lung injury

Walkey and Wiener. Macrolide antibiotics and survival in patients with acute lung injury.

Chest 2012;141:1153–9

http://dx.doi.org/10.1378/chest.11-1908

Previous work on animal models has suggested that macrolides may have therapeutic value for patients with acute lung injury because of their immuno-modulatory properties. This is a secondary analysis of data from a multicentre RCT on acute respiratory distress syndrome and management of acute lung injury (ALI). 47 out of 235 patients (20%) received a macrolide antibiotic within 24 hours of trial enrolment, most commonly erythromycin (57%) and then azithromycin (40%). Median duration of macrolide use was 4 days (IQR 2–8 days). 11 of the 47 patients (23%) died, compared with 67 of the 188 (36%) who did not receive a macrolide [P = 0.11]. Those patients given macrolides were more likely to have pneumonia as an ALI risk factor and were less likely to have non-pulmonary sepsis. After confounder adjustment, macrolide use was associated with lower 180-day mortality [hazard ratio (HR) 0.46; 95% CI 0.23 — 0.92; P = 0.028] and shorter time to successful discontinuation of mechanical ventilation [HR 1.93; 95% CI 1.18 — 3.17; P = 0.009]. Interestingly, fluoroquinolone (n = 90) and cephalosporins (n = 93) were not associated with improved outcomes. However, given that this was a secondary analysis, these results do need to be interpreted with caution and confirmed in a further RCT…

China has a serious epidemic of drug-resistant TB

Zhao et al. National survey of drug-resistant tuberculosis in China.

New Engl J Med 2012;366:2161–70

http://www.nejm.org/doi/full/10.1056/NEJMoa1108789

This national survey of drug-resistant tuberculosis (TB) was funded by the Chinese Ministry of Health. The authors used cluster-randomised sampling of TB cases, and testing for resistance to first-line (i.e. isoniazid, rifampicin, ethambutol and streptomycin) and second-line (i.e. ofloxacin and kanamycin) anti-TB drugs, to estimate the proportion of multidrug-resistant (MDR) TB cases — defined as resistance to at least isoniazid and rifampicin. Using published estimates of TB incidence, they then estimated the national incidence of MDR TB disease. A sample of 3037 new TB cases and 892 previously treated cases showed MDR in 5.7% [95% CI 4.5 — 7.0] and 25.6% [95% CI 21.5 — 29.8] of cases, respectively. 8% of the MDR cases had extensive drug resistance, defined as resistance to at least isoniazid, rifampicin, ofloxacin and kanamycin. Nationally there were 110,000 incident cases [95% CI 97,000 — 130,000] of MDR TB and 8,200 incident cases [95% CI 7,200 — 9,700] of extensive drug-resistant TB in 2007. Patients with multiple treatments having had their last treatment in a specialist TB hospital were at highest risk of MDR disease [OR 13.3; 95% CI 3.9 — 46.0]. The authors state that the problem is due to inadequate treatment in both the public health and hospital system, especially the TB hospitals. There is clearly much work to be done.

How good was the 2009 H1N1 influenza vaccine in preventing pandemic influenza?

Simpson et al. Effectiveness of H1N1 vaccine for the prevention of pandemic influenza in Scotland, UK; a retrospective observational cohort study.

Lancet 2012;online 26th June 2012.

http://dx.doi.org/10.1016/S1473-3099(12)70133-0

These authors used a retrospective observational cohort study design to assess the effectiveness of the 2009 H1N1 influenza vaccine in Scotland, UK. Data were obtained from primary care, hospital records, death certificates and virology swab results. Vaccine effectiveness was estimated by establishing the risk of hospital admission and death due to H1N1 influenza in both vaccinated and unvaccinated patients, and by using data on laboratory-confirmed cases of H1N1 in a subset of patients, whilst adjusting for confounders. H1N1 influenza vaccination was given to 38,926 out of 247,178 people (15.5% [95%CI 15.4 — 15.6]) between Oct 2009 and January 2010. There were 5207 emergency hospital admissions and 579 deaths in the unvaccinated population, and 924 hospital admissions and 71 deaths in the vaccinated population. The effectiveness of the H1N1 vaccination in preventing emergency hospital admissions from influenza-related disorders was 19.5% [95% CI 0.8 — 34.7] and its effectiveness in preventing laboratory-confirmed influenza was 77.0% [95% CI 2.0 — 95.0]. The H1N1 2009 influenza vaccine was therefore associated with substantial protection against pandemic influenza and a reduction in hospital admissions from influenza-related disorders in Scotland during the 2009–2010 pandemic.

Sleep disorders

CPAP and its effects on the incidence of hypertension and cardiovascular events in patients with asymptomatic obstructive sleep apnoea

Barbe et al. Effect of continuous positive airway pressure on the incidence of hypertension and cardiovascular events in non-sleepy patients with obstructive sleep apnoea: a randomised controlled trial.

JAMA 2012;307:2161–8

http://dx.doi.org/10.1001/jama.2012.4366

Continuous positive airway pressure (CPAP) is the standard treatment for symptomatic obstructive sleep apnoea (OSA). But what about those patients with sleep-disordered breathing who are asymptomatic? This was a multicentre parallel-group RCT of CPAP (n = 357) versus control (n = 366) in 723 patients with a raised apnoea-hypopnea index but with an Epworth Sleepiness Scale score of 10 or less. Primary outcome measures were hypertension (BP>140/90 mm Hg or requirement for hypertensive medication) or a cardiovascular (CVS) event (non-fatal MI, stroke, TIA, hospitalisation for unstable angina or arrhythmia, heart failure or CVS death). Follow-up was for a median of 4 years (IQR 2.7 — 4.4 years). 68 patients in the CPAP group developed new hypertension and 28 had CVS events, whereas 79 patients in the control group developed new hypertension and 31 had CVS events. The incidence ratio between the two groups was 0.83 [95% CI 0.63 — 1.1]. Therefore, in patients with OSA but without daytime sleepiness, CPAP did not result in a statistically significant reduction in hypertension or CVS events. But the wide confidence intervals suggest (as the authors admit) that the study may have been underpowered to detect a significant difference. And whether one should treat asymptomatic OSA is a moot point.

Obstructive sleep apnoea is being underdiagnosed in primary care patients with type II diabetes

Heffner et al. Prevalence of diagnosed sleep apnea among

patients with type 2 diabetes in primary care.

Chest 2012;141:1414–21

http://dx.doi.org/10.1378/chest.11-1945

The prevalence of obstructive sleep apnoea (OSA) in patients with type 2 diabetes has been reported to be between 54% and 94%. This is a US retrospective multicentre primary care study which aimed to assess primary care physicians' diagnosis of OSA in patients with type 2 diabetes managed in primary care clinics. 16,066 patients were identified who had made one or more visits to their primary care practice during an 18-month period. The overall prevalence of OSA was 18%, rising to 23% in obese diabetic patients. Using a multivariate logistic regression model, being male, a raised BMI, co-morbidity, lower LDL and HbA1C levels were associated with an OSA diagnosis [likelihood ratio, X2 = 1.713; P < 0.0001]. The authors conclude that primary care providers underdiagnose OSA in patients with type 2 diabetes, and that obese men with co-morbidities are more likely to receive a diagnosis of OSA. We are encouraged to be more aware of OSA and to implement OSA screening tools during primary care consultations.

Fibrotic lung disease

The value of randomised controlled trials: treatment with combination prednisone, azathioprine and N-acetylcysteine for idiopathic pulmonary fibrosis is unsafe and of no benefit

The Idiopathic Pulmonary Fibrosis Clinical Research Network. Prednisone, azathioprine, and N-acetlcysteine for pulmonary fibrosis.

New Engl J Med 2012;366:1968–77

http://www.nejm.org/doi/full/10.1056/NEJMoa1113354

This study is an excellent example of why clinical interventions — in this case, the widely used but non evidence-based triple combination of prednisolone, azathioprine and N-acetylcysteine (NAC) for the treatment of idiopathic pulmonary fibrosis (IPF) — should always be submitted to the methodological rigour of a randomised controlled trial (RCT). This was a randomised double-blind, placebo-controlled RCT in patients with mild to moderate IPF who were assigned in equal numbers to one of three groups: triple combination therapy, NAC alone, or placebo. The primary outcome was change in FVC over the planned 60-week treatment period. However, a planned interim analysis when approximately 50% of data had been collected (77 patients in the combination group; 78 in the placebo group) showed no clinical benefit from combination therapy. In addition, the combination group had a higher rate of death [8 vs 1; P = 0.01] and hospitalisation [23 vs 7; P < 0.001] than the placebo group. The triple combination therapy arm was therefore terminated by the independent safety monitoring board at a mean follow-up of 32 weeks. The NAC-only and placebo groups were continued. This is clear evidence against the use of triple therapy combination for IPF.

Miscellaneous

No significant increase in cardiovascular serious adverse events with varenicline use

Prochaska and Hilton. Risk of cardiovascular serious adverse events associated with varenicline use for tobacco cessation: systematic review and meta-analysis.

BMJ 2012;344:e2856

http://dx.doi.org/10.1136/bmj.e2856

This systematic review and meta-analysis is very reassuring. Medline, the Cochrane Library, online clinical trials registries and article reference lists were searched for randomised controlled trials (RCTs) which reported adverse events when comparing varenicline with inactive controls. Treatment-related cardiovascular disease (CVD) serious adverse events were defined as those occurring during drug treatment or within 30 days of discontinuation, and included any ischaemic or arrhythmic adverse CVD events such as myocardial infarction (MI), unstable angina, bypass grafting, arrhythmias, transient ischaemic attacks (TIAs), stroke, sudden death or CVD-related death, and congestive heart failure. 22 double-blinded placebo-controlled trials were identified; two included patients with active CVD and 11 had participants with a history of CVD. Rates of CVD serious adverse events were 0.63% (34/5431) in the varenicline groups and 0.47% (18/3801) in the placebo groups. The summary estimate for the risk difference of 0.27% [95% CI −0.10 − 0.63; P = 0.15], based on all 22 trials, was neither clinically nor statistically significant. Odds ratios based on the 14 trials with at least one CVD event also showed a non-significant difference between varenicline and placebo. Therefore, there's no evidence of increased CVD risk following varenicline treatment — which is good news.

Increased public awareness and brief training in general practice improves x-ray referral and lung cancer diagnosis rates

Athey et al. Early diagnosis of lung cancer: evaluation of a community-based social marketing intervention.

Thorax 2012;67:412–17

http://dx.doi.org/10.1136/thoraxjnl-2011-200714

This is an interesting report of a public awareness campaign combined with a brief educational intervention in general practices piloted in six localities in the UK with a high lung cancer incidence. Primary endpoints were self-reported awareness of lung cancer symptoms, intention to seek health care, chest x-ray referral rates, trends in the incidence of lung cancer, and stage at lung cancer diagnosis pre- and post-intervention. 128 out of 600 in the targeted population (21%; 95% CI 18 — 25) recalled the campaign. Compared with a responder in the control area, a responder in the intervention area was 1.97 times [95% CI 1.18 — 3.31] more likely to visit their GP and request an x-ray for a cough. Chest x-ray referral rates increased by 20% in the targeted practices in the year following the intervention versus a 2% fall in the control practices, which was highly significant [incidence rate ratio (IRR) 1.22; 95% CI 1.12 −1.33]. There was a 27% increase in lung cancer diagnosis in the intervention area versus the control area [IRR 1.52; 95% CI 0.83 — 2.44]. The authors conclude that an awareness campaign and early recognition initiative may facilitate lung cancer diagnosis.

Using pulse oximetry to screen for congenital heart disease in asymptomatic newborn babies

Thangaratinam et al. Pulse oximetry screening for congenital heart defects in asymptomatic newborn babies: a systematic review and meta-analysis.

Lancet 2012;379:2459–64

http://dx.doi.org/10.1016/S0140-6736(12)60107-X

Screening for congenital heart defects is an essential part of a newborn baby check; if, for example, a heart murmur is heard on auscultation then further investigations follow. Early recognition of congenital heart disease provides the prospect of improved outcomes. This systematic review assessed the performance of pulse oximetry as a screening method for detecting critical congenital heart defects in asymptomatic newborn babies. The authors screened 552 studies. 13 studies with data on 229,421 newborn babies met the inclusion criteria. The overall sensitivity of pulse oximetry for detection of critical congenital heart defects was 76.5% [95% CI 67.7 — 83.5] and the specificity was 99.9% [95% CI 99.7 — 99.9]. The false positive rate was 0.14% [95% CI 0.06 — 0.33], but this was much reduced when performed ≥ 24 hours versus < 24 hours after birth (0.05% [95% CI 0.02 — 0.12] vs. 0.50% [95% CI 0.29 — 0.86]; P=0.0017). The authors conclude that pulse oximetry is highly specific and moderately sensitive for the detection of critical congenital heart defects, and therefore that it meets the criteria for universal screening. Yet another role for pulse oximetry in the future?

Further evidence for primary care use of a respiratory diagnostic support service

Lucas et al. Diagnostic accuracy of primary care asthma/COPD working hypotheses, a real life study.

Resp Med 2012;106:1158–63

http://dx.doi.org/10.1016/j.rmed.2012.03.002

How to provide high quality diagnostic spirometry in primary care is the subject of ongoing debate. A 4-year audit of primary care referrals to a centralised nurse-led/respiratory specialist community-based respiratory assessment unit in west London, UK was published recently [see http://dx.doi.org/10.4104/pcrj.2012.00013]. These authors from Maastricht in The Netherlands investigated the working hypotheses of 17 GPs who referred 284 patients with respiratory problems to an ‘Asthma/COPD (AC) support service’, which provided high quality spirometry and medical history assessment by consultant pulmonologists. 49% of the referrals were based on clinical information only, 21% had had office spirometry performed, and in 30% of cases there was additional specialist information available. 50% of the working hypotheses were confirmed by the AC support service; but a working hypothesis of asthma was confirmed more frequently (62%) than a working hypothesis of COPD (40%). The authors conclude that a respiratory diagnostic support service is required in order to optimise primary care diagnosis of patients with respiratory problems. Very similar conclusions to the authors of the UK paper…