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Chronic obstructive pulmonary disease (COPD) and lung cancer are major lung diseases affecting millions worldwide. Both diseases have links to cigarette smoking and exert a considerable societal burden. People suffering from COPD are at higher risk of developing lung cancer than those without, and are more susceptible to poor outcomes after diagnosis and treatment. Lung cancer and COPD are closely associated, possibly sharing common traits such as an underlying genetic predisposition, epithelial and endothelial cell plasticity, dysfunctional inflammatory mechanisms including the deposition of excessive extracellular matrix, angiogenesis, susceptibility to DNA damage and cellular mutagenesis. In fact, COPD could be the driving factor for lung cancer, providing a conducive environment that propagates its evolution. In the early stages of smoking, body defences provide a combative immune/oxidative response and DNA repair mechanisms are likely to subdue these changes to a certain extent; however, in patients with COPD with lung cancer the consequences could be devastating, potentially contributing to slower postoperative recovery after lung resection and increased resistance to radiotherapy and chemotherapy. Vital to the development of new-targeted therapies is an in-depth understanding of various molecular mechanisms that are associated with both pathologies. In this comprehensive review, we provide a detailed overview of possible underlying factors that link COPD and lung cancer, and current therapeutic advances from both human and preclinical animal models that can effectively mitigate this unholy relationship.

Introduction: Severe cutaneous adverse drug reactions (SCARs) are not uncommon and potentially lifethreatening. Our objective is to study the patient characteristics, the pattern of implicated drugs and treatment outcome among patients with SCARs., Methods: A 10-year retrospective analysis of SCARs cases in Penang General Hospital was carried out from January 2006 to December 2015. Data collection is based on the Malaysian Adverse Drug Reactions Advisory Committee registry and dermatology clinic records., Results: A total of 189 cases of SCARs were encountered (F:M ratio; 1.2:1.0; mean age of 45 year). The commonest manifestation was Stevens-Johnson Syndrome [SJS] (55.0%), followed by toxic epidermal necrolysis [TEN] (23.8%), drug rash with eosinophilia and systemic symptoms [DRESS] (12.7%), acute generalised exanthematous pustulosis [AGEP] (4.8%), SJS/TEN overlap syndrome (2.6%) and generalised bullous fixed drug eruptions [GBFDE] (1.1%). Mean time to onset for TEN/SJS/Overlap syndrome was 10.5±13 days; AGEP, three days; GBFDE, 2.5±0.7 days, and DRESS, 29.4±5.7 days. The most common drugs implicated were antibiotics (33.3%), followed by allopurinol (18.9%) and anticonvulsant (18.4%). Out of 154 cases of SJS/TEN/overlap syndrome, allopurinol was the commonest causative agents (20.1%). In DRESS, allopurinol accounts for 45.8% of the cases. The mortality rate in SJS, TEN and DRESS were 1.9%, 13.3% and 12.5% respectively. No mortality was observed in AGEP and GBFDE., Conclusion: The commonest manifestations of SCARs in our setting were SJS, TEN and DRESS. Allopurinol was the most common culprit. Thus, judicious allopurinol use is advocated and pre-emptive genetic screening for HLAB *5801 should be considered.

Rationale: Domiciliary oxygen therapy (DOT) is commonly prescribed for patients with interstitial lung disease (ILD) and hypoxemia, although evidence supporting benefit is limited., Objectives: The aim of this study was to explore perspectives of respiratory physicians about DOT in patients with ILD., Methods: A qualitative study was undertaken with 26 respiratory physicians from Australia. Interviews were transcribed verbatim and coded independently by two investigators. Themes were established by consensus., Results: Physicians reported symptomatic relief as the main indication for prescribing DOT in ILD. Concerns were raised regarding the applicability of current clinical guidelines for DOT to ILD. Compared with patients with other lung diseases, there was a lower threshold for DOT prescription for patients with ILD. Physicians perceived that patients with ILD complied better with recommended DOT prescription. There was significant variation in infrastructure for oxygen assessment and prescription, patient support, and equipment provision among institutions and states. Various patients' attitudes and experiences toward DOT were reported, but most notable was physicians' perception of significant anxiety in most patients using DOT because of social stigma and concerns that DOT signified end-stage disease., Conclusions: Oxygen therapy was primarily prescribed for symptomatic management in patients with ILD. Education provision and supports regarding DOT varied significantly.

Background and Objective: Ambulatory oxygen therapy is often provided to patients with interstitial lung disease (ILD). Lightweight portable oxygen concentrators (POCs) provide an alternative to traditional portable systems such as compressed oxygen cylinders; however, their efficacy in patients with ILD has not been assessed. This study aimed to evaluate the clinical performance of three ambulatory oxygen systems (two different POCs and a compressed oxygen cylinder) during 6-min walk tests (6MWTs) in patients with ILD and exertional desaturation., Methods: A total of 20 participants with ILD of varying aetiologies who demonstrated exertional desaturation to <90% on room air during 6MWT were recruited. Each participant performed two 6MWTs while breathing room air. On a subsequent day, two further 6MWTs were performed, in random order: one breathing oxygen via a POC (either the Inogen One G2 POC or the EverGo POC at the setting of 6) and one with a compressed oxygen cylinder (at 5 L/min)., Results: There were no significant differences in nadir oxygen saturation (SpO 2 ) during 6MWTs using different portable oxygen devices (Trial 1: mean SpO 2 for Inogen One G2 POC: 82.3 ± 3.5% vs oxygen cylinder: 80.3 ± 2.2%, P = 0.14; Trial 2: mean SpO 2 for EverGo POC: 85.7 ± 7.7% vs oxygen cylinder: 86.1 ± 6.1%, P = 0.79). The mean 6-min walk distances were not significantly different among the three devices., Conclusion: The performance of the Inogen One G2 POC and the EverGo POC had comparable performance with that of the compressed oxygen cylinder during walking in patients with ILD and exertional desaturation., (© 2017 Asian Pacific Society of Respirology.)

Rationale: Domiciliary oxygen therapy is commonly prescribed for patients with interstitial lung disease and hypoxemia, either at rest or during exertion, with the aim of improving symptoms and functional status., Objectives: This study aimed to explore perspectives of adults with interstitial lung disease about domiciliary oxygen therapy, comparing insights from patients using and not using oxygen therapy., Methods: A qualitative study using semistructured interviews was undertaken on 24 adults residing in and near Melbourne, Australia who had a diagnosis of interstitial lung disease and met the Thoracic Society of Australia and New Zealand guidelines for domiciliary oxygen therapy. Study subjects included individuals who were oxygen-naive (n = 12) and oxygen-experienced (n = 12). Interviews were transcribed verbatim and coded independently by two investigators in accordance with the grounded theory method of analysis. Themes were established by consensus., Results: Patients using domiciliary oxygen therapy described widespread variation in usage. Oxygen-naive patients expected oxygen therapy to relieve dyspnea, whereas oxygen-experienced patients emphasized the benefits of oxygen on other, non-dyspnea-related physical symptoms. Practical and psychosocial challenges of using oxygen therapy were raised by both groups of patients., Conclusions: This study highlights the different expectations and experiences of domiciliary oxygen therapy for adults with interstitial lung disease. It is important to understand and address patients' concerns about the use of oxygen therapy for these patients.

Background: Home polysomnography (PSG) is an alternative method for diagnosis of obstructive sleep apnoea (OSA). Some types 3 and 4 PSG do not monitor sleep and so rely on patients' estimation of total sleep time (TST)., Aim: To compare patients' subjective sleep duration estimation with objective measures in patients who underwent type 2 PSG for probable OSA., Methods: A prospective clinical audit of 536 consecutive patients of one of the authors between 2006 and 2013. A standard questionnaire was completed by the patients the morning after the home PSG to record the time of lights being turned off and estimated time of sleep onset and offset. PSG was scored based on the guidelines of the American Academy of Sleep Medicine., Results: Median estimated sleep latency (SL) was 20 min compared with 10 min for measured SL (P < 0.0001). There was also a significant difference between the estimated and measured sleep offset time (median difference = -1 min, P = 0.01). Estimated TST was significantly shorter than the measured TST (median difference = -18.5 min, P = 0.002). No factors have been identified to affect patients' accuracy of sleep perception. Only 2% of patients had a change in their diagnosis of OSA based on calculated apnoea-hypopnoea index., Conclusions: Overall estimated TST in the patients with probable OSA was significantly shorter than measured with significant individual variability. Collectively, inaccurate sleep time estimation had not resulted in significant difference in the diagnosis of OSA., (© 2015 Royal Australasian College of Physicians.)

Background: Both low-molecular-weight heparin (LMWH) and unfractionated heparin (UFH) have been shown to be equivalent in efficacy and safety profiles for the management of pulmonary embolism (PE)., Aims: To assess the real world management of anticoagulation in PE in a tertiary hospital setting., Methods: An audit of patients with a new diagnosis of PE from March 2011 to March 2012. Data collected included patient demographics, anticoagulant, complication, mortality, time to first administration, frequency of monitoring and dose adjustment for UFH, time to therapeutic range for UFH (based on activated partial thromboplastin time) and length of hospital stay., Results: Of the 211 patients who were included, 139 were admitted through the Emergency Department, and 45 were managed with UFH. There was no significant difference in time to initial dose between those treated with LMWH and UFH (192 vs 98 min, P = 0.16). For UFH, average time to therapeutic range was 594 min (range 87–2257 min). During the course of UFH therapy, only 22% of activated partial thromboplastin time was within therapeutic range, while 44% was above and 33% was below therapeutic range. Average number of UFH dose adjustment was 5. Increasing weight and higher baseline fibrinogen levels significantly delayed time to therapeutic range for patients on UFH (P = 0.02 and 0.04 respectively). Up to 18 months following PE, overall mortality rate was 28%, with no significant difference between LMWH and UFH (28% vs 29%)., Conclusion: PE was predominantly managed with LMWH. UFH was suboptimally managed when used, although there was no impact on mortality rate.

Improved diagnostic sensitivity of bronchsocopy for the investigation of peripheral pulmonary lesions (PPLs) with the use of radial probe endobroncial ultrasound (EBUS) has been reported, although diagnostic performance varies considerably. A systematic review of published literature evaluating radial probe EBUS accuracy was performed to determine point sensitivity and specificity, and to construct a summary receiver-operating characteristic curve. Sub-group analysis and linear regression was used to identify possible sources of study heterogeneity. 16 studies with 1,420 patients fulfilled inclusion criteria. Significant inter-study variation in EBUS method was noted. EBUS had point specificity of 1.00 (95% CI 0.99-1.00) and point sensitivity of 0.73 (95% CI 0.70-0.76) for the detection of lung cancer, with a positive likelihood ratio of 26.84 (12.60-57.20) and a negative likelihood ratio of 0.28 (0.23-0.36). Significant inter-study heterogeneity for sensitivity was observed, with prevalence of malignancy, lesion size and reference standard used being possible sources. EBUS is a safe and relatively accurate tool in the investigation of PPLs. Diagnostic sensitivity of EBUS may be influenced by the prevalence of malignancy in the patient cohort being examined and lesion size. Further methodologically rigorous studies on well-defined patient populations are required to evaluate the generalisability of our results.

Background: Airway microcirculation is abnormal in asthma but the role of vascular changes in asthma deteriorations remains poorly defined. We prospectively assessed the vascular changes accompanying worsening of asthma control by using an inhaled corticosteroid (ICS) dose-reduction model., Objectives: To evaluate airway vascularity, vascular permeability and expression of vascular endothelial growth factor (VEGF) in early asthma deterioration induced by ICS back-titration., Methods: Twenty mild-to-moderate persistent symptomatic asthmatics on low-to-moderate ICS were recruited and treated with 4 weeks of high-dose fluticasone propionate (1000 microg/day) to achieve symptom control. This was followed by dose reduction to half of the pre-study doses for 4-8 weeks until the symptoms began to return. Endobronchial biopsy and bronchoalveolar lavage (BAL) samples were obtained after both treatment periods., Results: Vascularity as measured by the number and size of blood vessels, as well as VEGF expression did not change following ICS reduction. Even on high-dose ICS, perivascular albumin staining and BAL microalbumin levels in asthmatic subjects, as markers of permeability, were elevated when compared with normal subjects and both further increased significantly after ICS reduction. There was a significant association between changes in vascular leakiness and clinical deterioration. Increases in airway albumin correlated with previously reported increases in airway wall infiltration with T lymphocytes., Conclusions: Our results suggest that airway vascular leakage is a major pathophysiologic feature of early asthma deterioration, occurring before recrudescence of cellular inflammation.

Background: Back-titration of inhaled corticosteroid (ICS) dose in well-controlled asthma patients is emphasized in clinical guidelines, but there are few published data on the airway cell and cytokine changes in relation to ICS reduction. In our study, 20 mild-to-moderate persistent (inspite of low-moderate dose ICS treatment) asthmatic subjects prospectively rendered largely asymptomatic by high-dose ICS were assessed again by clinical, physiological, and airway inflammatory indices after 4-8 weeks of reduced ICS treatment. We aimed at assessing the underlying pathological changes in relation to clinical deterioration., Methods: Patients recorded daily symptom scores and peak expiratory flows (PEF). Spirometry and airways hyperreactivity (AHR) were measured and bronchoscopy was performed with assessment of airway biopsies (mast cells, eosinophils, neutrophils, and T lymphocytes), bronchoalveolar lavage (BAL) IL-5 and eotaxin levels and cellular profiles at the end of high-dose ICS therapy and again after ICS dose reduction. Baseline data were compared with symptomatic steroid-free asthmatics (n=42) and non-asthmatic controls (n=28)., Results: After ICS reduction, subjects experienced a variable but overall significant increase in symptoms and reductions in PEF and forced expiratory volume in 1 s. There were no corresponding changes in AHR or airways eosinophilia. The most relevant pathogenic changes were increased CD4(+)/CD8(+) T cell ratio, and decreased sICAM-1 and CD18 macrophage staining (potentially indicating ligand binding). However, there was no relationship between the spectrum of clinical deterioration and the changes in cellular profiles or BAL cytokines., Conclusions: These data suggest that clinical markers remain the most sensitive measures of early deterioration in asthma during back-titration of ICS, occurring at a time when AHR and conventional indices of asthmatic airway inflammation appear unchanged. These findings have major relevance to management and to how back-titration of ICS therapy is monitored.