Chronic obstructive pulmonary disease (COPD) encompasses a group of disorders characterised by the presence of incompletely reversible airflow obstruction with overlapping subsets of different phenotypes including chronic bronchitis, emphysema or asthma. The aim of this study was to determine the proportion of adult subjects aged >50 years within each phenotypic subgroup of COPD, defined as a post-bronchodilator ratio of forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC) <0.7, in accordance with current international guidelines.
Adults aged >50 years derived from a random population-based survey undertook detailed questionnaires, pulmonary function tests and chest CT scans. The proportion of subjects in each of 16 distinct phenotypes was determined based on combinations of chronic bronchitis, emphysema and asthma, with and without incompletely reversible airflow obstruction defined by a post-bronchodilator FEV1/FVC ratio of 0.7.
A total of 469 subjects completed the investigative modules, 96 of whom (20.5%) had COPD. Diagrams were constructed to demonstrate the relative proportions of the phenotypic subgroups in subjects with and without COPD. 18/96 subjects with COPD (19%) had the classical phenotypes of chronic bronchitis and/or emphysema but no asthma; asthma was the predominant COPD phenotype, being present in 53/96 (55%). When COPD was defined as a post-bronchodilator FEV1/FVC less than the lower limit of normal, there were one-third fewer subjects with COPD and a smaller proportion without a defined emphysema, chronic bronchitis or asthma phenotype.
This study provides proportional classifications of the phenotypic subgroups of COPD which can be used as the basis for further research into the pathogenesis and treatment of this heterogeneous disorder.
Little is known about the long-term outcomes of individuals with mild chronic obstructive pulmonary disease (COPD) as defined by the Global Initiative for Chronic Obstructive Lung Disease (GOLD).
A population cohort of 6671 randomly selected adults without asthma was stratified into categories of modified GOLD-defined COPD (prebronchodilator spirometry). Further stratification was based on the presence or absence of respiratory symptoms. After 11 years, associations between baseline categories of COPD and decline in forced expiratory volume in 1 s (FEV
At baseline, modified GOLD criteria were met by 610 (9.1%) participants, 519 (85.1%) of whom had stage 1 COPD. At follow-up, individuals with symptomatic stage 1 COPD (n = 224) had a faster decline in FEV1 (–9 ml/year (95% CI –13 to –5)), increased respiratory care utilisation (OR 1.6 (95% CI 1.0 to 2.6)) and a lower quality of life than asymptomatic subjects with normal lung function (n = 3627, reference group). In contrast, individuals with asymptomatic stage 1 COPD (n = 295) had no significant differences in FEV1 decline (–3 ml/year (95% CI –7 to +1)), respiratory care utilisation (OR 1.05 (95% CI 0.63 to 1.73)) or quality of life scores compared with the reference group.
In population-based studies, respiratory symptoms are of major importance for predicting long-term clinical outcomes in subjects with COPD with mild obstruction. Population studies based on spirometry only may misestimate the prevalence of clinically relevant COPD.
The incremental shuttle walking test (ISWT) is used to assess exercise capacity in patients with chronic obstructive pulmonary disease (COPD) and is employed as an outcome measure for pulmonary rehabilitation. This study was designed to establish the minimum clinically important difference for the ISWT.
372 patients (205 men) performed an ISWT before and after a 7-week outpatient pulmonary rehabilitation programme. After completing the course, subjects were asked to identify, from a 5-point Likert scale, the perceived change in their exercise performance immediately upon completion of the ISWT. The scale ranged from "better" to "worse".
The mean (SD) age was 69.4 (8.4) years, forced expiratory volume in 1 s (FEV1) 1.06 (0.53) l and FEV1/forced vital capacity (FVC) ratio 50.8 (18.1)%. The baseline shuttle walking test distance was 168.5 (114.6) m which increased to 234.7 (125.3) m after rehabilitation (mean difference 65.9 m (95% CI 58.9 to72.9)). In subjects who felt their exercise tolerance was "slightly better" the mean improvement was 47.5 m (95% CI 38.6 to 56.5) compared with 78.7 m (95% CI 70.5 to 86.9) in those who reported that their exercise tolerance was "better" and 18.0 m (95% CI 4.5 to 31.5) in those who felt their exercise tolerance was "about the same".
Two levels of improvement were identified. The minimum clinically important improvement for the ISWT is 47.5 m. In addition, patients were able to distinguish an additional benefit at 78.7 m.
To determine whether well trained lay people could deliver asthma self-management education with comparable outcomes to that achieved by primary care based practice nurses.
Randomised equivalence trial.
39 general practices in West London and North West England.
567 patients with asthma who were on regular maintenance therapy. 15 lay educators were recruited and trained to deliver asthma self-management education.
An initial consultation of up to 45 min offered either by a lay educator or a practice based primary care nurse, followed by a second shorter face to face consultation and telephone follow-up for 1 year.
Unscheduled need for healthcare.
Patient satisfaction and need for courses of oral steroids.
567 patients were randomised to care by a nurse (n = 287) or a lay educator (n = 280) and 146 and 171, respectively, attended the first face to face educational session. During the first two consultations, management changes were made in 35/146 patients seen by a practice nurse (24.0%) and in 56/171 patients (32.7%) seen by a lay educator. For 418/567 patients (73.7%), we have 1 year data on use of unscheduled healthcare. Under an intention to treat approach, 61/205 patients (29.8%) in the nurse led group required unscheduled care compared with 65/213 (30.5%) in the lay led group (90% CI for difference –8.1% to 6.6%; 95% CI for difference –9.5% to 8.0%). The 90% CI contained the predetermined equivalence region (–5% to +5%) giving an inconclusive result regarding the equivalence of the two approaches. Despite the fact that all patients had been prescribed regular maintenance therapy, 122/418 patients (29.2%) required courses of steroid tablets during the course of 1 year. Patient satisfaction following the initial face to face consultation was similar in both groups.
It is possible to recruit and train lay educators to deliver a discrete area of respiratory care, with comparable outcomes to those seen by nurses.
NCT00129987
About 5–10% of patients with asthma suffer from poorly controlled disease despite corticosteroid (CS) treatment, which may indicate the presence of CS insensitivity. A study was undertaken to determine whether relative CS insensitivity is present in alveolar macrophages from patients with severe asthma and its association with p38 mitogen-activated protein kinase (MAPK) activation and MAPK phosphatase-1 (MKP-1).
Fibreoptic bronchoscopy and bronchoalveolar lavage (BAL) were performed in 20 patients with severe asthma and 19 with non-severe asthma and, for comparison, in 14 normal volunteers. Alveolar macrophages were exposed to lipopolysaccharide (LPS, 10 µg/ml) and dexamethasone (10–8 and 10–6 M). Supernatants were assayed for cytokines using an ELISA-based method. p38 MAPK activity and MKP-1 messenger RNA expression were assayed in cell extracts.
The inhibition of LPS-induced interleukin (IL)1β, IL6, IL8, monocyte chemotactic protein (MCP)-1 and macrophage inflammatory protein (MIP)-1 release by dexamethasone (10–6 M) was significantly less in macrophages from patients with severe asthma than in macrophages from patients with non-severe asthma. There was increased p38 MAPK activation in macrophages from patients with severe asthma. MKP-1 expression induced by dexamethasone and LPS, expressed as a ratio of LPS-induced expression, was reduced in severe asthma.
Alveolar macrophages from patients with severe asthma demonstrate CS insensitivity associated with increased p38 MAPK activation that may result from impaired inducibility of MKP-1.
The indication for chest physical therapy as an adjunct to the treatment of children hospitalised with acute pneumonia remains controversial and there is a lack of robust scientific evidence for the effectiveness of this modality in these patients.
A randomised controlled trial was conducted in two tertiary hospitals in southern Brazil. Children aged 29 days to 12 years hospitalised with pneumonia between February and October 2006 were recruited; 51 were randomly allocated to the intervention group (chest physical therapy plus standard treatment for pneumonia) and 47 to the control group (standard treatment for pneumonia alone). The primary outcome was time to clinical resolution. The secondary outcomes were length of stay in hospital and duration of respiratory symptoms and signs.
There were no significant differences in terms of median time to clinical resolution (4.0 vs 4.0 days, p = 0.84) and median length of hospital stay (6.0 vs 6.0 days, p = 0.76) between the intervention and control groups. The intervention group had a longer median duration of coughing (5.0 vs 4.0 days, p = 0.04) and of rhonchi on lung auscultation (2.0 vs 0.5 days, p = 0.03) than the control group.
Chest physical therapy as an adjunct to standard treatment does not hasten clinical resolution of children hospitalised with acute pneumonia and may prolong duration of coughing and rhonchi.
Idiopathic pulmonary fibrosis (IPF) is a chronic progressive disorder with a poor prognosis. Epithelial instability is a crucial step in the development and progression of the disease, including neoplastic transformation. Few tissue markers for epithelial instability have been reported in IPF. Squamous cell carcinoma antigen (SCCA) is a serine protease inhibitor typically expressed by dysplastic and neoplastic cells of epithelial origin, more often in squamous cell tumours. At present, no information is available on its expression in IPF.
SCCA and transforming growth factor β (TGFβ) expression in surgical lung biopsies from 22 patients with IPF and 20 control cases was examined. An in vitro study using A549 pneumocytes was also conducted to investigate the relationship between SCCA and TGFβ expression. SCCA and TGFβ epithelial expression was evaluated by immunohistochemistry and reverse transcription–PCR (RT-PCR). SCCA values were correlated with different pathological and clinical parameters. Time course analysis of TGFβ expression in A549 pneumocytes incubated with different SCCA concentrations was assessed by real time RT–PCR.
SCCA was expressed in many metaplastic alveolar epithelial cells in all IPF cases with a mean value of 24.9% while it was seen in only two control patients in up to 5% of metaplastic cells. In patients with IPF, SCCA correlated positively with extension of fibroblastic foci (r = 0.49, p = 0.02), expression of TGFβ (r = 0.78, p<0.0001) and with carbon monoxide transfer factor decline after 9 months of follow-up (r = 0.59, p = 0.01). In vitro experiments showed that incubation of cultured cells with SCCA induced TGFβ expression, with a peak at 24 h.
Our findings provide for the first time a potential mechanism by which SCCA secreted from metaplastic epithelial cells may exert a profibrotic effect in IPF. SCCA could be an important biomarker in this incurable disease.
Childhood obstructive sleep apnoea (OSA) is increasingly being recognised. Its effects on blood pressure (BP) elevation and hypertension are still controversial.
To evaluate the association between OSA and ambulatory BP in children.
Children aged 6–13 years from randomly selected schools were invited to undergo overnight sleep study and ambulatory BP monitoring after completing a validated OSA questionnaire. OSA was diagnosed if the obstructive apnoea–hypopnoea index (AHI) was >1, and normal controls had AHI <1 and snoring <3 nights per week. Children with OSA were subdivided into a mild group (AHI 1–5) and moderate to severe group (AHI >5).
306 subjects had valid sleep and daytime BP data. Children with OSA had significantly higher BP than normal healthy children during both sleep and wakefulness. BP levels increased with the severity of OSA, and children with moderate to severe disease (AHI >5) were at significantly higher risk for nocturnal systolic (OR 3.9 (95% CI 1.4 to 10.5)) and diastolic (OR 3.3 (95% CI 1.4 to 8.1)) hypertension. Multiple linear regression revealed a significant association between oxygen desaturation index and AHI with daytime and nocturnal BP, respectively, independent of obesity.
OSA was associated with elevated daytime and nocturnal BP, and is an independent predictor of nocturnal hypertension. This has important clinical implications as childhood elevated BP predicts future cardiovascular risks. Future studies should examine the effect of therapy for OSA on changes in BP.
A Th1 predominant immune response has been shown in acute hypersensitivity pneumonitis. Predominance of Th2 appears to favour the development of pulmonary fibrosis through the profibrotic process and has been described as crucial in the progression of idiopathic pulmonary fibrosis. Chronic bird fancier’s lung (cBFL) can present with a histological pattern of usual interstitial pneumonia (UIP)-like lesions. Little is known about the Th1/Th2 balance in the pathogenesis of cBFL.
To evaluate the relevance of Th1-type chemokines (interferon-inducible protein, IP-10) and Th2-type chemokines (thymus- and activation-regulated chemokine, TARC) and their receptors (CXCR3 and CCR4) to the histological patterns of cBFL, 40 patients with cBFL who underwent surgical lung biopsies, 12 with acute BFL (aBFL) and 10 healthy volunteers were analysed. IP-10 and TARC levels in serum and bronchoalveolar lavage (BAL) fluid were measured by ELISA. Immunohistochemistry for CXCR3 and CCR4 was performed on surgical lung specimens.
The ratio of TARC to IP-10 in the serum of patients with UIP-like lesions was significantly higher than in patients with cNSIP/OP-like lesions, aBFL and healthy volunteers. The ratio of CCR4 to CXCR3 in patients with UIP-like lesions was significantly higher than in those with cNSIP/OP-like lesions and fNSIP-like lesions. The ratio of CCR4-positive to CXCR3-positive cells correlated with the ratio of TARC to IP-10 in serum.
A Th2 predominant immune response may play an important role in the development of UIP-like lesions, as already observed in idiopathic pulmonary fibrosis. A Th1 predominance may play a role in the development of cNSIP/OP-like lesions in cBFL.
To target preventive strategies in old age, which of the very elderly are predisposed to developing lower respiratory tract infections was investigated.
Prospective observational follow-up study.
General population.
Unselected cohort of 587 participants aged 85 years in Leiden, The Netherlands.
As reported in the literature, predictive factors were selected and assessed at baseline. During a 5 year follow-up period, information on the development of lower respiratory tract infections was obtained from general practitioners or nursing home physicians. Associations between predictive factors were analysed with Cox regression, and population attributable risks were calculated.
The incidence of lower respiratory tract infections among persons aged 85–90 years was 94 (95% CI 80–108) per 1000 person years. After multivariate analysis, history of chronic obstructive pulmonary disease (COPD), smoking, oral glucocorticosteroid use, severe cognitive impairment, history of stroke and declined functional status remained independently associated with the occurrence of lower respiratory tract infections. Smoking was the greatest contributor with a population attributable risk of 32%.
In the very old, smoking, COPD, stroke and declined functional status were associated with the occurrence of lower respiratory tract infections and provide a means of targeting patients at risk of severe health complications.
Impaired development in utero is suggested to increase the risk of poor respiratory health in adulthood, although a consensus has not been reached. A possible explanation for discrepancies between previous studies is inconsistent controlling for potential confounding factors, particularly childhood infections. Also, little is known regarding the relative importance of factors operating at different stages of the lifecourse. We have used detailed longitudinal data from the Newcastle Thousand Families cohort to assess the impact of birth weight, and various other factors acting throughout the lifecourse, on predicting forced expiratory volume in 1 s (FEV1).
Detailed information was collected prospectively during childhood, including birth weight, childhood infections and socioeconomic circumstances. At age 49–51 years, 412 study members attended for clinical examination and measurement of FEV1. These data were analysed in relation to a range of factors from across the lifecourse using linear regression models.
After adjustment for all other significant variables, increasing birth weight, standardised for sex and gestational age (p = 0.011), being breast fed for more than 4 weeks (p = 0.017), less frequent childhood lower respiratory tract infections (LRTI) (p = 0.015), non- smoking (p<0.001), lower body fat percentage (p = 0.010), male sex (p<0.001), no history of asthma (p = 0.013) and greater adult height (p<0.001) were all independently associated with higher adult FEV1.
Adult lung function is influenced by numerous factors during an individual’s lifetime, acting both directly and indirectly throughout the lifecourse. As expected, sex, height and smoking were the most important predictors of FEV1, but birth weight, breast feeding and childhood LRTIs also contributed significantly.