Early chronic obstructive pulmonary disease: Beyond spirometry

The significant healthcare burden associated with chronic obstructive pulmonary disease(COPD) is driving us to improve our understanding of the natural history of this disease. Historically, the focus has been largely centred on diagnosing and treating individuals with moderate and severe disease. However, it is now recognised that the speed of decline in lung function as measured by forced expiratory volume in 1 s occurs faster in the earlier stages of the disease process. As a result, a clearer understanding of the potential benefits of treatment in early COPD is needed. It is recognised that many patients with COPD remain undiagnosed in the community which has prompted global case-finding initiatives. In this review we discuss the difficulties in diagnosing COPD in its early stages, examine the roleof case-finding and look at the evidence for early intervention with therapeutic agents. There is a growing interest in the phenotypic variation amongst patients with COPD and we explore the role of phenotyping in early COPD and its potential benefits in providing a more individualised approach to COPD management. The majority of patients with COPD are known to die from non-respiratory causes such as cardiovascular disease. The mechanistic link is thought to relate to systemic inflammation, causing us to question whether earlier interventions could have a beneficial impact on the burden of co-morbidities for patients with COPD.

Role of chronic obstructive pulmonary disease in lung cancer pathogenesis

Chronic obstructive pulmonary disease(COPD) and lung cancer are two important smoking related conditions. However, COPD has been shown to be an independent risk factor for lung cancer regardless of smoking history, suggesting that COPD and lung cancer may share a common pathogenesis. This review summarizes the epidemiology of lung cancer and COPD briefly, as well as discussing the potential for shared genetic risk, and shared genomic mechanisms, such as epigenetic changes or DNA damage induced by smoking. How key areas of COPD pathogenesis, such as inflammation, oxidative stress and protease imbalance may contribute to subsequent development of cancer will also be covered. Finally the possibility that consequences of COPD, such as hypoxia, influence carcinogenesis will be reviewed. By understanding the pathogenesis of COPDand lung cancer in detail it is possible that new treatments may be developed and the risk of lung cancer in COPD may be reduced.

Diagnosis and treatment of subsegmental pulmonary embolism

Subsegmental pulmonary embolism(SSPE) affects the 4 th division and more distal pulmonary arterial branches. SSPE can be isolated or affect multiple subsegments, be symptomatic or incidental(unsuspected) and may or may not be associated with deep vein thrombosis. Symptoms, clinical risk scores and biomarkers are less sensitive for diagnosing SSPE compared to more central pulmonary embolism. The diagnosis is confirmed using radiological imaging,predominately computed tomographic pulmonary angiogram(CTPA) or ventilation/perfusion scanning. The increasing utilization of CTPAs may have resulted in overdiagnosis driven by smaller pulmonary emboli. There is insufficient evidence of improved mortality or reduced venous thromboembolism recurrence with anticoagulation treatment for SSPE however,the major and clinically significant haemorrhage risks are well described. As the resolution of diagnostic imaging has improved, we may be viewing the natural physiological filtering process performed by the lungs that may not require treatment.

Personalising exacerbation prediction strategies in chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease(COPD)is one of the leading causes of mortality and morbidity worldwide.One of the most important features of this disease is exacerbations where a patient’s respiratory symptoms episodically worsen.Exacerbations accounted for over 140000 hospital admissions in 2012 in the United Kingdom with considerably more exacerbations being treated in primary care.Despite significant research in this area in recent years,treatment of acute exacerbations in the community remains limited to oral glucocorticoids,antibiotics and bronchodilators.One of the issues with unpicking the complexity of exacerbations is trying to find out the exact underlying cause and mechanism that leads to symptoms and lung destruction.Currently symptoms are initially guided by symptoms alone though multiple causes of exacerbations have common presentations.This includes viral and bacterial infections and episodes relating to environmental triggers such as pollen and pollution.There is also evidence that cardiovascular factors can contribute to symptoms of breathlessness that can mimic COPD exacerbations.In this editorial we discuss recent advances in the use of precision medicine to more accurately treat exacerbations of COPD.This includes identification of phenotypes that could help rationalise treatment and more importantly identify novel drug targets.We also consider the future role of precision medicine in preventing exacerbations and identifying COPD patients that are at increased risk of developing them.

Managing panniculitis in alpha-1 antitrypsin deficiency: Systematic review of evidence behind treatment

AIM To systematically review literature for management of alpha-1 antitrypsin deficiency(AATD) panniculitis. METHODS Multiple databases were searched using combinations of pertinent terms. Articles were selected describing panniculitis treatment in patients with AAT < 11 μmol and/or PiZZ genotype, with no language limitation. All relevant articles were accessed in full text. Independent review of abstracts and full manuscripts was conducted by 2 reviewers, and quality assessment by one reviewer(checked by a second). Data extraction was conducted byone reviewer(checked by a second). Narrative synthesis only was conducted, as data were unsuitable for metaanalysis.RESULTS Thirty-two case reports and 4 case series were found. Augmentation therapy(infusions of plasma-derived AAT) was the most successful, with complete resolution of symptoms in all patients. Dapsone is a less expensive option, and it achieved clinical resolution in 62% of patients, but it is very poorly tolerated. Among other single-agent antibiotics, doxycycline was the most successful with complete clinical resolution seen in 33% of patients. Immunosuppressants were largely unsuccessful; 80% of patients exhibited no response. Liver transplantation and therapeutic plasma exchange displayed complete resolution in 66% of patients. Other strategies, such as non-steroidal anti-inflammatory drugs or antibiotics other than dapsone did not show sufficient response rates to recommend their use. Authors note the risk of bias imposed by the type of evidence(case reports, case series) available in this field.CONCLUSION Dapsone is the recommended first line therapy for AATD panniculitis, followed by augmentation therapy. Plasma exchange may be an alternative in the setting of rapidly progressive disease.