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BackgroundPatients with chronic obstructive pulmonary disease (COPD) are at increased risk of cardiovascular disease (CVD). The extent to which the excess CVD risk is captured by risk factors in QRISK, a widely used CVD risk scoring tool, is not well studied.MethodsWe created an incidence cohort of diagnosed COPD patients from the United Kingdom (UK) Clinical Practice Research Datalink GOLD database (January 1998–July 2018). The outcome was a composite of fatal or non-fatal CVD events. Sex-specific age-standardised incidence ratios (SIR) were compared with values for the UK primary-care population. The observed 10-year CVD risk was derived using the Kaplan-Meier estimator and was compared with predicted 10-year risk from the QRISK3 tool.Results13 208 patients (mean age 64.9 years, 45% women) were included. CVD incidence was 3.53 events per 100 person-years. The SIR of CVD was 1.71 (95% CI 1.61 to 1.75) in women and 1.62 (95%CI 1.54–1.64) in men. SIR was particularly high among patients younger than 65 years (women=2.13 (95% CI 1.94 to 2.19); men=1.86 (95% CI 1.74 to 1.90)). On average, the observed 10-year risk was 52% higher than QRISK predicted score (33.5% vs 22.1%). The difference was higher in patients younger than 65 years (observed risk 82% higher than predicted).ConclusionPeople living with COPD are at a significantly heightened risk of CVD over and beyond their predicted risk. This is particularly the case for younger people whose 10-year CVD risk can be >80% higher than predicted. Risk scoring tools must be validated and revised to provide accurate CVD predictions in patients with COPD.

The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures.

Chronic obstructive pulmonary disease (COPD) is diagnosed on the basis of airflow obstruction, although the definition also encompasses emphysema. It develops when someone with an (often undefined) genetic susceptibility encounters sufficient inhaled triggers. Genetic susceptibility is complex and determined by multiple alleles; α1-antitrypsin deficiency is the best example of genetic risk. Cigarette smoke is the most common trigger in high-income countries, but globally important contributors include the burning of biomass fuel in under-ventilated spaces, and systematic disadvantage across the life-course affecting lung growth and development. The natural history of lung function decline and maximal lung function attainment is fundamental to understanding COPD. In individuals susceptible to the effects of smoke, the pulmonary inflammatory response is qualitatively and quantitatively different from that in non-susceptible individuals. Once established, inflammation persists even after exposure has ceased. Airflow obstruction in COPD results from a combination of airway wall inflammatory response, luminal mucus accumulation, destruction of small airways and loss of alveolar–airway attachments from emphysema. The major symptoms are breathlessness, cough and sputum expectoration. Breathlessness is multifactorial, but primarily driven by hyperinflation. Although progressive airflow obstruction is the hallmark of COPD, other outcomes are also important, notably exacerbations and the development of co-morbidities.

Persistent ill health after acute COVID-19—referred to as long COVID, the post-acute COVID-19 syndrome, or the post-COVID-19 condition—has emerged as a major concern. We undertook an international consensus exercise to identify research priorities with the aim of understanding the long-term effects of acute COVID-19, with a focus on people with pre-existing airways disease and the occurrence of new-onset airways disease and associated symptoms. 202 international experts were invited to submit a minimum of three research ideas. After a two-phase internal review process, a final list of 98 research topics was scored by 48 experts. Patients with pre-existing or post-COVID-19 airways disease contributed to the exercise by weighting selected criteria. The highest-ranked research idea focused on investigation of the relationship between prognostic scores at hospital admission and morbidity at 3 months and 12 months after hospital discharge in patients with and without pre-existing airways disease. High priority was also assigned to comparisons of the prevalence and severity of post-COVID-19 fatigue, sarcopenia, anxiety, depression, and risk of future cardiovascular complications in patients with and without pre-existing airways disease. Our approach has enabled development of a set of priorities that could inform future research studies and funding decisions. This prioritisation process could also be adapted to other, non-respiratory aspects of long COVID.

BackgroundThis review aims to synthesise available evidence on the prevalence of chronic obstructive pulmonary disease (COPD), associated risk factors, hospitalisations and COPD readmissions in Africa.MethodUsing the Met-Analyses and Systematic Reviews of Observational Studies guideline, electronic databases were searched from inception to 1 October 2021. The quality of studies was assessed using the Newcastle-Ottawa Scale. Evidence from retrieved articles was synthesised, and a random-effect model meta-analysis was conducted. The protocol was registered on PROSPERO.ResultsThirty-nine studies met the inclusion criteria, with 13 included in the meta-analysis. The prevalence of COPD varied between the Global Initiative for Chronic Obstructive Lung Disease (2%–24%), American Thoracic Society/European Respiratory Society (1%–17%) and Medical Research Council chronic bronchitis (2%–11%) criteria, respectively. Increasing age, wheezing and asthma were consistent risk factors for COPD from studies included in the narrative synthesis. Our meta-analysis indicated that prior tuberculosis ((OR 5.98, 95% CI 4.18 to 8.56), smoking (OR 2.80, 95% CI: 2.19 to 3.59) and use of biomass fuel (OR 1.52, 95% CI: 1.39 to 1.67)) were significant risk factors for COPD. Long-term oxygen therapy (HR 4.97, 95% CI (1.04 to 23.74)) and frequent hospitalisation (≥3 per year) (HR 11.48, 95% CI (1.31 to 100.79)) were risk factors associated with 30-day COPD readmission.ConclusionThis study not only highlights specific risk factors for COPD risk in Africa but also demonstrates the paucity and absence of research in several countries in a continent with substantial COPD-related mortality. Our findings contribute towards the development of evidence-based clinical guidelines for COPD in Africa.PROSPERO registration numberCRD42020210581.

Exacerbations of chronic obstructive pulmonary disease are important events to people living with this condition and a common cause of emergency hospital admission. In the absence of a confirmatory biomarker, an exacerbation remains a clinical diagnosis of exclusion and clinicians must be alert to alternative diagnoses. Most exacerbations are caused by airway infection, particularly with respiratory viruses. The mainstay of exacerbation treatment is an increase in the dose and/or frequency of short-acting beta-agonists, with short-course oral corticosteroids and/or antibiotics. Although there have been no new interventions to treat exacerbations in many years, there is still much variation in care and opportunity to improve outcomes. There has been a new focus on both the management of comorbidities and the optimisation of future care to reduce the risk of further events. This review summarises advances in managing exacerbations of chronic obstructive pulmonary disease, focusing on hospitalised patients.

BackgroundThe COPD Best Practice Tariff (BPT) is a pay-for-performance scheme in England that incentivises review by a respiratory specialist within 24 hours of admission and completion of a list of key care components prior to discharge, known as a discharge bundle, for patients admitted with acute exacerbation of COPD (AECOPD). We investigated whether the two components of the COPD BPT were associated with lower 30-day mortality and readmission in people discharged following AECOPD.MethodsLongitudinal study of national audit data containing details of AECOPD admissions in England and Wales between 01 February 2017 and 13 September 2017. Data were linked with national admissions and mortality data. Mixed-effects logistic regression, using a random intercept for hospital to adjust for clustering of patients, was used to determine the relationship between the COPD BPT criteria (combined and separately) and 30-day mortality and readmission. Models were adjusted for age, sex, socioeconomic status, length of stay, smoking status, Charlson comorbidity index, mental illness and requirement for oxygen or noninvasive ventilation during admission.Results28 345 patients discharged from hospital following AECOPD were included. 37% of admissions conformed to the two COPD BPT criteria. No relationship was observed between BPT conforming admissions and 30-day mortality (OR: 1.09 (95% CI 0.92 to 1.29)) or readmissions (OR: 0.96 (95% CI 0.90 to 1.02)). No relationship was observed between either of the individual COPD BPT components and 30-day mortality or readmissions. However, a specialist review at any time during admission was associated with lower inpatient mortality (OR: 0.69 (95% CI 0.58 to 0.81)).ConclusionCompletion of the combined COPD BPT criteria does not appear associated with a reduction in 30-day mortality or readmission. However, specialist review was associated with reduced inpatient mortality. While it is difficult to argue that discharge bundles do not improve care, this analysis questions whether the pay-for-performance model improves mortality or readmissions.

ObjectivesTo determine growth outcomes at 11 years of age in children born <27 weeks of gestation in England in 2006 (EPICure2) and to compare growth from birth to 11 years of age for births<26 weeks with those in England in 1995 (EPICure).Methods200 EPICure2 children assessed at 11 years alongside 143 term-born controls. Growth measures from birth to 11 years were compared for births<26 weeks between EPICure2 (n=112) and EPICure (n=176). Growth parameter z-scores were derived from 1990 UK standards.ResultsAmong EPICure2 children, mean z-scores for height and weight were close to the population standards (0.08 and 0.18 SD, respectively) but significantly below those of controls: difference in mean (Δ) z-scores for weight −0.42 SD (95% CI −0.68 to –0.17), for height −0.45 SD (−0.70 to –0.20) and for head circumference (HC) −1.05 SD (−1.35 to –0.75); mean body mass index (BMI) z-score in EPICure2 children was 0.18 SD, not significantly different from controls (0.43 SD, p=0.065). Compared with EPICure, EPICure2 children born <26 weeks at 11 years had higher z-scores for weight (Δ 0.72 (0.47, 0.96)), height (Δ 0.55 (0.29, 0.81)) and BMI (Δ 0.56 (0.24, 0.87)), which were not fully explained by perinatal/demographic differences between eras. Weight catch-up was greater from term-age to 2.5/3 years in EPICure2 than in EPICure (1.25 SD vs 0.53 SD; p<0.001). Poor HC growth was observed in EPICure2, unchanged from EPICure.ConclusionsSince 1995, childhood growth in weight, height and BMI have improved for births <26 weeks of gestation, but there was no improvement in head growth.

The impact of COVID-19 on physical and mental health and employment after hospitalisation with acute disease is not well understood. The aim of this study was to determine the effects of COVID-19-related hospitalisation on health and employment, to identify factors associated with recovery, and to describe recovery phenotypes.

Guidelines are critical for facilitating cost-effective COPD care. Development and implementation in low-and middle-income countries (LMICs) is challenging. To guide future strategy, an overview of current global COPD guidelines is required.

ObjectiveTo investigate whether size at birth and growth trajectories in infancy and childhood are associated with determinants of cardiovascular and metabolic risks in young adults born extremely preterm (EP, <26 weeks of gestation).MethodsWe used longitudinal data from the EPICure study of 129 EP survivors up to 19 years in the UK and Ireland in 1995. Determinants of cardiovascular and metabolic risks at 19 years included the presence of metabolic syndrome, body mass index (BMI) and systolic blood pressure (SBP). Predictors were birth weight for gestation and gain in weight z-scores in the following periods: birth–postmenstrual age of 40 weeks (term), infancy (term–2.5 years), early childhood (2.5–6.0 years) and late childhood (6–11 years).ResultsMetabolic syndrome was present in 8.7% of EP participants at 19 years. Compared with subjects without metabolic syndrome, those with metabolic syndrome tended to have a smaller size at birth (difference in means: −0.55 SD, 95% CI −1.10 to 0.01, p=0.053) and a greater increase in weight z-scores from term to 2.5 years (difference in means: 1.00 SD, 95% CI −0.17 to 2.17, p=0.094). BMI at 19 years was positively related to growth from 2.5 to 6.0 years ([Formula]: 1.03, 95% CI 0.31 to 1.75, p=0.006); an inverse association with birthweight z-scores was found in the lower socioeconomic status group ([Formula]: −1.79, 95% CI −3.41 to –0.17, p=0.031). Central SBP was positively related to growth from 2.5 to 6.0 years ([Formula]: 1.75, 95% CI 0.48 to 3.02, p=0.007).ConclusionSize at EP birth and increased catch-up in weight from 2.5 to 6.0 years were associated with BMI and central SBP in early adulthood.

ObjectiveTo determine whether improvements in school age outcomes had occurred between two cohorts of births at 22–25 weeks of gestation to women residents in England in 1995 and 2006.DesignLongitudinal national cohort studies.SettingSchool-based or home-based assessments at 11 years of age.ParticipantsEPICure2 cohort of births at 22–26 weeks of gestation in England during 2006: a sample of 200 of 1031 survivors were evaluated; outcomes for 112 children born at 22–25 weeks of gestation were compared with those of 176 born in England during 1995 from the EPICure cohort. Classroom controls for each group acted as a reference population.Main outcome measuresStandardised measures of cognition and academic attainment were combined with parent report of other impairments to estimate overall neurodevelopmental status.ResultsAt 11 years in EPICure2, 18% had severe and 20% moderate impairments. Comparing births at 22–25 weeks in EPICure2 (n=112), 26% had severe and 21% moderate impairment compared with 18% and 32%, respectively, in EPICure. After adjustment, the OR of moderate or severe neurodevelopmental impairment in 2006 compared with 1995 was 0.76 (95% CI 0.45 to 1.31, p=0.32). IQ scores were similar in 1995 (mean 82.7, SD 18.4) and 2006 (81.4, SD 19.2), adjusted difference in mean z-scores 0.2 SD (95% CI −0.2 to 0.6), as were attainment test scores. The use of multiple imputation did not alter these findings.ConclusionImprovements in care and survival between 1995 and 2006 are not paralleled by improved cognitive or educational outcomes or a reduced rate of neurodevelopmental impairment.

Chronic obstructive pulmonary disease (COPD) is a physiological diagnosis made on the basis of airflow obstruction. It develops when a genetically susceptible individual encounters sufficient inhaled environmental triggers. Genetic susceptibility is complex and determined by multiple alleles, with emphysema from α1-antitrypsin deficiency being a rare exception of well-described genetic risk. Cigarette smoke is the most common trigger in higher income countries, but globally the burning of biomass fuel in underventilated spaces is an important contributor to COPD. The natural history of lung function decline and maximal lung function attainment is fundamental to understanding COPD and still incompletely understood. In individuals susceptible to the effects of smoke, the airway inflammatory response is qualitatively and quantitatively different from that in non-susceptible individuals. Once established, inflammation persists even after exposure to smoke has ceased. Airflow obstruction in COPD results from a combination of airway wall inflammatory response, luminal mucus accumulation and loss of alveolar–airway attachments from emphysema. The major symptoms of COPD are breathlessness, cough and sputum expectoration. Breathlessness is casually multifactorial, with a contribution from dynamic hyperinflation. Although progressive airflow obstruction is the hallmark of COPD, it is recognized that other outcomes are also important, notably exacerbations and the development of co-morbidities.

Interventions to prevent the spread of SARS-CoV-2 have been associated with substantial reductions in exacerbations of airways diseases, likely through reduced transmission of other respiratory viruses. We surveyed 4442 people with airways disease (asthma=3627, bronchiectasis=258, chronic obstructive pulmonary disease=557) to gauge attitudes and intentions towards continuing such measures after the COVID-19 pandemic. 47% intended to continue wearing a face mask in indoor public spaces, and 61% thought everyone should be required to do so during the ‘influenza season. Women, those with bronchiectasis, and older people were generally more cautious. Respiratory virus infection control measures should be considered in clinical guidelines and public health recommendations.

ObjectiveTo investigate growth trajectories from age 2.5 to 19 years in individuals born before 26 weeks of gestation (extremely preterm; EP) compared with term-born controls.MethodsMultilevel modelling of growth data from the EPICure study, a prospective 1995 birth cohort of 315 EP participants born in the UK and Ireland and 160 term-born controls recruited at school age. Height, weight, head circumference and body mass index (BMI) z-scores were derived from UK standards at ages 2.5, 6, 11 and 19 years.Results129 (42%) EP children were assessed at 19 years. EP individuals were on average 4.0 cm shorter and 6.8 kg lighter with a 1.5 cm smaller head circumference relative to controls at 19 years. Relative to controls, EP participants grew faster in weight by 0.06 SD per year (95% CI 0.05 to 0.07), in head circumference by 0.04 SD (95% CI 0.03 to 0.05), but with no catch-up in height. For the EP group, because of weight catch-up between 6 and 19 years, BMI was significantly elevated at 19 years to +0.32 SD; 23.4% had BMI >25 kg/m2and 6.3% >30 kg/m2but these proportions were similar to those in control subjects. EP and control participants showed similar pubertal development in early adolescence, which was not associated with height at 19 years in either study group. Growth through childhood was related to birth characteristics and to neonatal feeding practices.ConclusionsEP participants remained shorter and lighter and had smaller head circumferences than reference data or controls in adulthood but had elevated BMI.

Large numbers of people are being discharged from hospital following COVID-19 without assessment of recovery. In 384 patients (mean age 59.9 years; 62% male) followed a median 54 days post discharge, 53% reported persistent breathlessness, 34% cough and 69% fatigue. 14.6% had depression. In those discharged with elevated biomarkers, 30.1% and 9.5% had persistently elevated d-dimer and C reactive protein, respectively. 38% of chest radiographs remained abnormal with 9% deteriorating. Systematic follow-up after hospitalisation with COVID-19 identifies the trajectory of physical and psychological symptom burden, recovery of blood biomarkers and imaging which could be used to inform the need for rehabilitation and/or further investigation.

In the nineteenth century, it was recognised that acute attacks of chronic bronchitis were harmful. 140 years later, it is clearer than ever that exacerbations of chronic obstructive pulmonary disease (ECOPD) are important events. They are associated with significant mortality, morbidity, a reduced quality of life and an increasing reliance on social care. ECOPD are common and are increasing in prevalence. Exacerbations beget exacerbations, with up to a quarter of in-patient episodes ending with readmission to hospital within 30 days. The healthcare costs are immense. Yet despite this, the tools available to diagnose and treat ECOPD are essentially unchanged, with the last new intervention (non-invasive ventilation) introduced over 25 years ago.An ECOPD is ‘an acute worsening of respiratory symptoms that results in additional therapy’. This symptom and healthcare utility-based definition does not describe pathology and is unable to differentiate from other causes of an acute deterioration in breathlessness with or without a cough and sputum. There is limited understanding of the host immune response during an acute event and no reliable and readily available means to identify aetiology or direct treatment at the point of care (POC). Corticosteroids, short acting bronchodilators with or without antibiotics have been the mainstay of treatment for over 30 years. This is in stark contrast to many other acute presentations of chronic illness, where specific biomarkers and mechanistic understanding has revolutionised care pathways. So why has progress been so slow in ECOPD? This review examines the history of diagnosing and treating ECOPD. It suggests that to move forward, there needs to be an acceptance that not all exacerbations are alike (just as not all COPD is alike) and that clinical presentation alone cannot identify aetiology or stratify treatment.

A proportion of people living with common variable immunodeficiency disorders develop granulomatous-lymphocytic interstitial lung disease (GLILD). We aimed to develop a consensus statement on the definition, diagnosis, and management of GLILD. All UK specialist centers were contacted and relevant physicians were invited to take part in a 3-round online Delphi process. Responses were graded as Strongly Agree, Tend to Agree, Neither Agree nor Disagree, Tend to Disagree, and Strongly Disagree, scored +1, +0.5, 0, −0.5, and −1, respectively. Agreement was defined as greater than or equal to 80% consensus. Scores are reported as mean ± SD. There was 100% agreement (score, 0.92 ± 0.19) for the following definition: “GLILD is a distinct clinico-radio-pathological ILD occurring in patients with [common variable immunodeficiency disorders], associated with a lymphocytic infiltrate and/or granuloma in the lung, and in whom other conditions have been considered and where possible excluded.” There was consensus that the workup of suspected GLILD requires chest computed tomography (CT) (0.98 ± 0.01), lung function tests (eg, gas transfer, 0.94 ± 0.17), bronchoscopy to exclude infection (0.63 ± 0.50), and lung biopsy (0.58 ± 0.40). There was no consensus on whether expectant management following optimization of immunoglobulin therapy was acceptable: 67% agreed, 25% disagreed, score 0.38 ± 0.59; 90% agreed that when treatment was required, first-line treatment should be with corticosteroids alone (score, 0.55 ± 0.51).

BackgroundThere are limited data on the burden of cardiovascular comorbidities in people with bronchiectasis. Our cross-sectional study estimates the burden of pre-existing diagnoses of coronary heart disease (CHD) and stroke in people with bronchiectasis compared with the general population. The historical cohort study investigates if individuals with bronchiectasis are at increased risk of incident CHD and stroke events.MethodsWe used primary care electronic records from the Clinical Practice Research Datalink. The cross-sectional study used logistic regression to quantify the association between bronchiectasis and recorded diagnoses of CHD or stroke. Cox regression was used to investigate if people with bronchiectasis experienced increased incident CHD and strokes compared with the general population, adjusting for age, sex, smoking habit and other risk factors for cardiovascular disease.ResultsPre-existing diagnoses of CHD (OR 1.33, 95% CI 1.25 to 1.41) and stroke (OR 1.92, 95% CI 1.85 to 2.01) were higher in people with bronchiectasis compared with those without bronchiectasis, after adjusting for age, sex, smoking and risk factors for cardiovascular disease. The rate of first CHD and stroke were also higher in people with bronchiectasis (HR for CHD 1.44 (95% CI 1.27 to 1.63) and HR for stroke 1.71 (95% CI 1.54 to 1.90)).ConclusionThe risk of CHD and stroke are higher among people with bronchiectasis compared with the general population. An increased awareness of these cardiovascular comorbidities in this population is needed to provide a more integrated approach to the care of these patients.

Chronic obstructive pulmonary disease (COPD) is a physiological diagnosis made on the basis of airflow obstruction. It develops when a genetically susceptible individual encounters a sufficient environmental trigger. Genetic susceptibility is complex and determined by multiple alleles, with the exception of emphysema caused by α1-antitrypsin deficiency. Cigarette smoke is the usual trigger in the developed world, but globally the burning of biomass fuel in underventilated spaces is important. In individuals susceptible to the effects of smoke, the airway inflammatory response is qualitatively and quantitatively different from that in non-susceptible subjects and is predominantly composed of neutrophils, macrophages and CD8+ lymphocytes. Once established, inflammation can persist even after exposure to smoke has ceased. Airflow obstruction in COPD results from a combination of the airway wall inflammatory response, luminal mucus accumulation and loss of alveolar–airway attachments from coexisting emphysema. The major symptoms are breathlessness, cough and phlegem. Breathlessness is multifactorial, with a contribution from dynamic hyperinflation. Although progressive airflow obstruction is the hallmark of COPD, it is now recognized that it has other important outcomes, notably exacerbations and the development of co-morbidities. In addition, some patient may develop COPD from a normal rate of decline in lung function following sub-maximal lung growth.

Many survivors of preterm birth will have abnormal lung development, reduced peak lung function and, potentially, an increased rate of physiological lung function decline, each of which places them at increased risk of chronic obstructive pulmonary disease across the lifespan. Current rates of preterm birth indicate that by the year 2040, around 50 years since the introduction of surfactant therapy, more than 700 million individuals will have been born prematurely—a number that will continue to increase by about 15 million annually. In this Personal View, we describe current understanding of the impact of preterm birth on lung function through the life course, with the aim of putting this emerging health crisis on the radar for the respiratory community. We detail the potential underlying mechanisms of prematurity-associated lung disease and review current approaches to prevention and management. Furthermore, we propose a novel way of considering lung disease after preterm birth, using a multidimensional model to determine individual phenotypes of lung disease—a first step towards optimising management approaches for prematurity-associated lung disease.

The success of whole-exome sequencing to identify mutations causing single-gene disorders has been well documented. In contrast whole-exome sequencing has so far had limited success in the identification of variants causing more complex phenotypes that seem unlikely to be due to the disruption of a single gene. We describe a family where two male offspring of healthy first cousin parents present a complex phenotype consisting of peripheral neuropathy and bronchiectasis that has not been described previously in the literature. Due to the fact that both children had the same problems in the context of parental consanguinity we hypothesised illness resulted from either X-linked or autosomal recessive inheritance. Through the use of whole-exome sequencing we were able to simplify this complex phenotype and identified a causative mutation (p.R1070*) in the gene periaxin (PRX), a gene previously shown to cause peripheral neuropathy (Dejerine–Sottas syndrome) when this mutation is present. For the bronchiectasis phenotype we were unable to identify a causal single mutation or compound heterozygote, reflecting the heterogeneous nature of this phenotype. In conclusion, in this study we show that whole-exome sequencing has the power to disentangle complex phenotypes through the identification of causative genetic mutations for distinct clinical disorders that were previously masked.

This Review summarises current knowledge on the pulmonary manifestations of primary antibody deficiency (PAD) syndromes in adults. We describe the major PAD syndromes, with a particular focus on common variable immunodeficiency (CVID). Respiratory infection is a common presenting feature of PAD syndromes. Respiratory complications are frequent and responsible for much of the morbidity and mortality associated with these syndromes. Respiratory complications include acute infections, the sequelae of infection (eg, bronchiectasis), non-infectious immune-mediated manifestations (notably the development of granulomatous-lymphocytic interstitial lung disease in CVID), and an increased risk of lymphoma. Although minor abnormalities are detectable in the lungs of most patients with CVID by CT scanning, not all patients develop lung complications. Mechanisms associated with the maintenance of lung health versus lung disease, and the development of bronchiectasis versus immune-mediated complications, are now being dissected. We review the investigation, treatment, and management strategies for PAD syndromes, and include key research questions relating to both infectious and non-infectious complications of PAD in the lung.

OBJECTIVE: Exacerbations of COPD requiring hospital admission have important clinical and societal implications. We sought to investigate the incidence, recurrence, risk factors, and mortality of patients with COPD exacerbations requiring hospital admission compared with those without hospital admission during 3-year follow-up. Patients with COPD (N = 2,138) were identified from the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) observational cohort.

Chronic obstructive pulmonary disease (COPD) is a physiological diagnosis made on the basis of airflow obstruction. It develops when a genetically susceptible individual encounters a sufficient environmental trigger. Genetic susceptibility is complex and determined by multiple alleles, aside from the model of emphysema caused by α-1 anti-trypsin deficiency. Cigarette smoke is the usual trigger in the developed world but globally the burning of biomass fuel in under-ventilated space is important. In those subjects genetically susceptible to the effects of smoke, there is an airway inflammatory response that is qualitatively and quantitatively different from non-susceptible subjects, predominantly composed of neutrophils, macrophages and CD8+ lymphocytes. Once established, the inflammation can persist even after exposure to smoke has ceased. Airflow obstruction in COPD results from a combination of the airway wall inflammatory response, luminal mucus, and loss of alveolar–airway attachments from co-existent emphysema. Although progressive airflow obstruction is the hallmark of COPD, it is now recognized that there are other important outcomes in this condition, notably exacerbations and the development of co-morbidities.

Comorbid ischemic heart disease (IHD) is a common and important cause of morbidity and mortality in patients with COPD. The impact of IHD on COPD in terms of a patient's health status, exercise capacity, and symptoms is not well understood.

Patients with COPD are at risk for cardiovascular events. This is attributed to increased systemic inflammation. The course of COPD is punctuated by exacerbations, which further increase systemic inflammation, but the risk of vascular events in the postexacerbation period has never been defined.