Single-night continuous positive airway pressure treatment improves blood fluid properties in individuals recently diagnosed with obstructive sleep apnoea.

Obstructive sleep apnoea (OSA) is a prevalent disorder that causes repetitive, temporary collapses of the upper airways during sleep, resulting in intermittent hypoxaemia and sleep fragmentation. Given those with OSA also exhibit decreased blood fluidity, this clinical population is at heightened risk for cardiovascular disease (CVD) development. Continuous positive airway pressure (CPAP) remains a primary therapy in OSA, which improves sleep quality and limits sleep fragmentation. While CPAP effectively ameliorates nocturnal hypoxic events and associated arousals, it remains unclear whether CVD risk factors are positively impacted. The aim of the present study was thus to assess the effects of an acute CPAP therapy on sleep quality and the physical properties of blood that determine blood fluidity. Sixteen participants with suspected OSA were recruited into the current study. Participants attended the sleep laboratory for two visits: an initial diagnostic visit that included confirmation of OSA severity and comprehensive assessments of blood parameters, followed by a subsequent visit where participants were administered an individualised, acute CPAP therapy session and had their blood assessments repeated. Holistic appraisal of blood rheological properties included assessment of blood and plasma viscosity, red blood cell (RBC) aggregation, deformability, and osmotic gradient ektacytometry. Acute CPAP treatment significantly improved sleep quality parameters, which were associated with decreased nocturnal arousals and improved blood oxygen saturation. Whole blood viscosity was significantly decreased following acute CPAP treatment, which might be explained by the improved RBC aggregation during this visit. Although an acute increase in plasma viscosity was observed, it appears that the alterations in RBC properties that mediate cell-cell aggregation, and thus blood viscosity, overcame the increased plasma viscosity. While deformability of RBC was unaltered, CPAP therapy had mild effects on the osmotic tolerance of RBC. Collectively, novel observations demonstrate that a single CPAP treatment session acutely improved sleep quality, which was accompanied by improved rheological properties.

Audit of clinical follow-up and complications after acute pulmonary embolism in an Australian Metropolitan Health Service.

We explored post-pulmonary embolism (post-PE) follow-up at a large Australian regional city hospital health service. Over a 12-month period, we identified 195 (49% male) patients with a median age of 62 years. Post-PE follow-up was not organised for 23 patients and delayed for seven patients. Post-PE complication occurred in 21% of all patients reviewed in the clinic after discharge. Follow-up imaging was arranged in 28% of patients. To deliver high-quality care, we recommend implementing a local post-PE follow-up pathway, which balances individual physician preference with available resources and expert recommendations.

Dysfunctional breathing treated with continuous positive airway pressure in newly diagnosed obstructive sleep apnoea: a prospective cohort study.

A prospective cohort study investigating patients with obstructive sleep apnoea (OSA) was conducted to determine the prevalence of dysfunctional breathing and if continuous positive airway pressure (CPAP) therapy improves associated symptoms. Almost half of newly diagnosed patients with OSA had dysfunctional breathing and CPAP was not an effective treatment. Dysfunctional breathing is common in patients with OSA.

Long-term oxygen therapy-related adverse outcomes resulting in hospitalisation: 3-year experience of an Australian metropolitan health service.

The aim of this study was to evaluate the incidence of long-term oxygen therapy (LTOT)-related adverse outcomes in our health service. LTOT patients retrospectively recruited had their medical records reviewed for the period of 1 January 2014 to 30 June 2018. Burns, physical injuries, any falls attributable to LTOT requiring admission were the outcomes measured. Of 291 patients, four patients required admission due to LTOT-related adverse events where three admissions were related to falls secondary to tripping over oxygen tubing.

Non-typeable Haemophilus Influenzae detection in the lower airways of patients with lung cancer and chronic obstructive pulmonary disease.

BACKGROUND: Chronic airway inflammation and hypersensitivity to bacterial infection may contribute to lung cancer pathogenesis. Previous studies have demonstrated that nontypeable Haemophilus influenzae (NTHi) is the most common colonizing bacteria in the lower airways of patients with COPD. The objective of this study was to determine the presence of NTHi and immunoglobulin concentrations in patients with lung cancer, COPD and controls. METHODS: Serum and bronchial wash samples were collected from patients undergoing diagnostic bronchoscopy. Total IgE, IgG and specific NTHi IgG were measured by enzyme linked immunosorbent assay. Bronchial wash samples were examined for the presence of NTHi via PCR. RESULTS: Out of the 60 patients: 20 had confirmed Lung Cancer, 27 had COPD only and 13 were used as Controls. NTHi was detected in the lower airways of all three groups (Lung Cancer 20%; COPD 22% and Controls 15%). Total IgE was highest in Lung Cancer subjects followed by COPD and control subjects (mean ± SD: 870 ± 944, 381 ± 442, 159 ± 115). Likewise total IgG was higher in Lung cancer (Mean ± SD: 6.99 ± 1.8) patients compared to COPD (Mean ± SD: 5.43 ± 2). CONCLUSIONS: The lack of difference in NTHi and specific antibodies between the three groups makes it less likely that NTHi has an important pathogenetic role in subjects with Lung Cancer. However the detection of higher IgE antibody in Lung Cancer subjects identifies a possible mechanism for carcinogenesis in these subjects and warrants further study.

Music reduces state anxiety scores in patients undergoing pleural procedures: a randomised controlled trial.

BACKGROUND: Patient anxiety is an often overlooked complication of pleural diagnostic and therapeutic procedures. Listening to music is effective in reducing patient anxiety in some endoscopy procedures but has not yet been evaluated in pleural procedures. AIM: To evaluate the benefits of music therapy during pleural procedures on a patient's anxiety, perceived pain and satisfaction with the procedure. METHODS: Consecutive patients undergoing therapeutic pleural procedures were randomised to music and control groups. Participants in the music group listened to self-selected music using ear-bud headphones for the duration of the procedure. State anxiety was assessed before and after the procedure using the State Trait Anxiety Inventory. Physiological parameters were also measured. RESULTS: Sixty patients were included in the study. In the music group, a reduction in state anxiety scores were observed post-procedure (34 ± 11 vs 48 ± 13, P < 0.001), while no change was observed in the control group (40 ± 11 vs 42 ± 11, P = 0.51). Participants in the music group had reductions in heart rate (87 ± 17 vs 95 ± 15, P = 0.04), systolic (121 ± 13 vs 130 ± 16, P = 0.02) and diastolic blood pressure (72 ± 8 vs 78 ± 9, P = 0.01) post procedure compared to the pre-procedures values. A similar change was not detected in the control group: heart rate (86 ± 17 vs 85 ± 15, P = 0.73), systolic (133 ± 21 vs 134 ± 20, P = 0.83) and diastolic blood pressure (77 ± 9 vs 79 ± 10, P = 0.30). There was no difference in patient pain scores (P = 0.8), willingness to undergo the procedure again (P= 0.27), satisfaction with the performance of the pleural procedure (P = 0.20) and duration of the procedure (P = 0.68) between the music and control groups. CONCLUSIONS: Listening to music appears to be beneficial in reducing anxiety in patients undergoing pleural procedures.

Increased QT dispersion is associated with reduced overall survival in patients with acute exacerbations of chronic obstructive pulmonary disease.

OBJECTIVES: Chronic obstructive pulmonary disease (COPD), especially acute exacerbations of COPD, are associated with increased cardiovascular mortality, including sudden cardiac death. Previous studies have reported that ECG abnormalities are common in stable COPD patients. However, the prognostic utility of ECG taken at the time of AECOPD is not known. In this study we sought to address this gap in knowledge pertaining to ECG parameters at time of AECOPD and overall survival. METHODS: We conducted a retrospective cohort study of patients admitted to our institution with a primary diagnosis of AECOPD. Standard 12-lead ECG obtained at the time of initial presentation was evaluated. The primary outcome was overall survival. RESULTS: Two hundred and eleven AECOPD patients were considered for the study. Death had occurred in 42 (20%) patients at follow-up. Among the different ECG parameters evaluated, the QT Dispersion (QTD) and corrected QT Dispersion (QTcD) were significantly associated with increased mortality. Receiver Operator Characteristic analysis identified QTcD >48msec had a sensitivity of 90% and specificity of 55% in predicting death and QTcD >48msec was also associated with worse overall survival (months) (mean ± SD: 26 ± 1.0 vs. 30 ± 0.7, p = 0.001). CONCLUSION: QTcD ≥48msec is associated with increased mortality. Further research is required to better understand this association and potentially identify reversible factors that if appropriately addressed, may ultimately improve the prognosis of patients with COPD.

Evaluation of platelet lymphocyte ratio and 90-day mortality in patients with acute exacerbation of chronic obstructive pulmonary disease.

BACKGROUND: Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) have high mortality and health care costs. The platelet to lymphocyte ratio (PLR) is a marker of inflammation and has been reported to be elevated in patients with AECOPD compared to stable state. In this study, we sought to evaluate the association of the PLR in patients with AECOPD with 90-day mortality. METHODS: We conducted a retrospective cohort study of patients admitted to our institution with a primary diagnosis of AECOPD between January 2014 and July 2014. Blood test results on admission were recorded. The primary outcomes were 90-day mortality. RESULTS: One hundred and eighty-one AECOPD patients were considered for the study. Death had occurred in 16 (9%) patients within 90 days of hospital discharge. Univariable analysis identified age, haemoglobin, neutrophil count, and urea level, neutrophil lymphocyte ratio (NLR) and PLR as being associated with increased 90-day mortality. Multivariable logistic regression analysis variables demonstrated that only PLR (P=0.03) was significantly associated with death at 90 days. Receiver operator characteristic analysis identified PLR ≥235 had a sensitivity of 63% and specificity of 74% in predicting 90-day mortality. PLR was ≥235 was also associated with worse survival (days) [mean ± standard deviation (SD): PLR ≥235 vs. PLR <235: 512±358 vs. 626±346, P=0.004]. CONCLUSIONS: A PLR ≥235 was significantly associated with 90-day mortality, which may provide prognostic guidance to clinicians.

Lung ultrasound B-lines in exacerbations of chronic obstructive pulmonary disease.

We report on preliminary observations on performing lung ultrasound (LUS) in patients admitted to hospital with an exacerbation of chronic obstructive pulmonary disease (COPD). We found that LUS had high specificity and moderate sensitivity in identifying patients with elevated B-type natriuretic peptide. Thus, we hypothesise that LUS may have utility in screening COPD patients with an exacerbation to identify the sub-group with elevated natriuretic peptides and are at risk of increased cardiovascular mortality. The use of LUS in patients with acute and chronic respiratory disorders is increasing and its role in COPD patients is an interesting subject for future research.

Malnutrition screening in patients admitted to hospital with an exacerbation of chronic obstructive pulmonary disease and its association with patient outcomes.

OBJECTIVES: There is a paucity of information on the prevalence and clinical implications of malnutrition in patients hospitalised for management of acute exacerbations of chronic obstructive pulmonary disease (AECOPD). This study aimed to fill this gap in knowledge. METHODS: We performed a retrospective observational cohort study of 100 hospitalised AECOPD patients. The Malnutrition Screening Tool (MST) was used to identify patients at risk of malnutrition (MST ≥2). Patient characteristics, length of stay, readmission rate, 12-month survival and overall survival were collected using a proforma. RESULTS: MST scores were available in 90 patients, of whom 22% of patients had a MST score of ≥2. There were no significant differences in COPD severity, treatment received and biochemical parameters between the groups of patients 'at risk of malnutrition' and those 'not at risk of malnutrition'. Length of stay in hospital was longer in patients 'at risk of malnutrition' (median (IQR): 3.5 (2-7.5) vs. 3.0 (1-5), p = 0.048). Overall survival was significantly reduced in patients with 'at risk of malnutrition' compared to those patients 'not at risk of malnutrition' (337 ± 245 vs. 670 ± 292, p < 0.001). CONCLUSIONS: Using the MST we found that one-fifths of our hospitalised AECOPD patients are at 'at risk of malnutrition'. Moreover, this cohort of patients had worse outcomes both during and extending beyond hospitalisation compared to patients 'not at risk of malnutrition'. Our study illustrates the need for routine malnutrition screening for hospitalised AECOPD patients because it has implications for potentially reducing morbidity and mortality in COPD.

Suboptimal inhaler medication adherence and incorrect technique are common among chronic obstructive pulmonary disease patients.

Patients with chronic obstructive pulmonary disease (COPD) are routinely prescribed one or more inhaled medications. Adherence to inhaler medications and correct inhaler device technique are crucial to successful COPD management. The goals of this study were to estimate adherence and inhaler technique in a cohort of COPD patients. This was an observational study conducted on a sample of 150 COPD patients. Medication adherence was assessed using the Medication Adherence Report Scale (MARS). Inhaler technique was assessed using standardized checklists. Clinical data were collected using a proforma. Of the 150 patients (mean age 70.3 years, 52% male), 58% reported suboptimal adherence (MARS ≤ 24). High adherence to therapy (MARS = 25) was associated with older age (p = 0.001), but not any of the other studied variables. Medication non-adherence was not associated with COPD exacerbations. Errors (≥ 1) in inhaler technique were common across all of the types of inhaler devices reportedly used by patients, with the highest proportion of errors among Turbuhaler users (83%) and the least proportion of errors among Handihaler users (50%). No clinical variables were associated with errors in inhaler technique. Suboptimal adherence and errors in inhaler technique are common among COPD patients. No clinical variables to assist in the prediction of medication non-adherence and poor inhaler technique were identifiable. Consequently, regular assessment of medication adherence and inhaler technique should be incorporated into routine clinical practice to facilitate improved health outcomes among patients with COPD.

Evaluation of the Patterns of Care Provided to Patients With COPD Compared to Patients With Lung Cancer Who Died in Hospital.

INTRODUCTION: There is limited information about the end-of-life care provided to patients with end-stage chronic obstructive pulmonary disease (COPD) in comparison to patients with lung cancer. AIM AND METHODS: We compared the end-of-life care provided to patients with COPD versus patients with lung cancer who died in hospital over a 12-month period in our institution. RESULTS: During the study period, 89 patients died due to COPD (n = 34) or lung cancer (n = 55). Compared to patients with lung cancer, patients with COPD received less palliative care services (50% vs 9%, P < .001) and underwent more diagnostic tests and received more life-prolonging measures. CONCLUSION: Toward the end of their life, patients with COPD received fewer symptom-alleviating treatments and palliative care services.

Misinterpreting risk and test results delays diagnosis in a patient with pulmonary embolism.

We report the case of a middle-aged man where a diagnosis of pulmonary embolism (PE) was delayed due to initial underestimation of risk and over-reliance on D-dimer testing. The patient presented with pleuritic chest pain after a 5 h domestic flight. The treating clinicians presumed that this duration of immobilisation was insufficient to cause a PE, D-dimer was not measured and the patient was discharged home. One week later, the patient re-presented due to persistence of chest pain. On this occasion, D-dimer was measured and it was normal, which was interpreted as excluding a PE. Subsequently, a CT pulmonary angiogram was performed, which demonstrated a subsegmental PE. This case highlights the importance of accurate assessment of PE-risk factors and following clinical guidelines, since a delayed diagnosis of PE is associated with increased mortality.

Lung adenocarcinoma masquerading as refractory Klebsiella pneumoniae.

We report the case of a middle-aged man where a diagnosis of Klebsiella pneumoniae obscured the underlying malignancy. The patient was hospitalised for management of a presumed refractory community-acquired pneumonia with radiological features of right lower lobe consolidation. Bronchoscopy did not identify an endobronchial lesion and washings grew K pneumoniae. CT-guided fine-needle aspirate samples did not detect any malignancy. However, despite appropriate antibiotic treatment there was no improvement in the patient's clinical condition. Consequently, a CT-guided lung core biopsy was performed to obtain more tissue for histopathology, which was diagnostic of primary lung adenocarcinoma. This case highlights the need to continue to investigate a patient who is not progressing as clinically appropriate to their original diagnosis.

Differences in care between general medicine and respiratory specialists in the management of patients hospitalized for acute exacerbations of chronic obstructive pulmonary disease.

CONTEXT: Hospitalized patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD) may be managed by either respiratory specialists (RS) or general medicine physicians (GMP). While previous studies have audited the hospital AECOPD management of RS, only a small number of studies have evaluated the management of GMP. AIMS: The aims of this study were to firstly examine the differences in AECOPD management of GMP and RS and secondly compare their care to national COPD guidelines. METHODS: A retrospective review was undertaken of consecutive AECOPD patients admitted to two hospitals (one hospital where all AECOPD patients were managed by RS and another where all AECOPD patients were managed by GMP) over a 3-month period. Electronic medical records, medical case notes, pathology and radiology data for the admission were reviewed. RESULTS: There were 201 COPD exacerbations in 169 patients (49.7% male, mean age 72.3). GMP managed 84 (41.7%) exacerbations. In comparison to RS, GMP performed fewer spirometry tests, blood gas analysis and less frequently treated patients with guideline-recommended medications. Referral to pulmonary rehabilitation was poor for both groups of clinicians. Median length of stay was shorter in GMP patients versus RS patients (3 days vs. 5 days, P = 0.001). There were no differences in the 12-month re-admission (41.7% vs. 38.5%, P = 0.664) and mortality rates (10.7% vs. 6%, P = 0.292) between both groups of patients. CONCLUSION: Our study found differences in the hospital AECOPD management of GMP and RS, but these did not translate into different clinical outcomes between their patients. We also found suboptimal adherence to national COPD guidelines, suggesting that there is scope for improvement in the AECOPD management of both groups of clinicians.

Metastatic small-cell lung cancer presenting as fulminant hepatic failure.

We report a case of a 75-year-old woman with fulminant hepatic failure due to metastatic small-cell lung cancer (SCLC). The patient was hospitalised for the management of rapidly progressive hepatic failure. Thoracic radiology identified a widened mediastinum, and prior to hospitalisation she had received antibiotics for a urinary tract infection. Consequently, her hepatic failure was deemed to be due to either sarcoidosis with hepatic involvement or an antibiotic-related adverse event and was treated with prednisolone. However, the patient's clinical condition continued to deteriorate and a liver biopsy was obtained. Histopathology and immunohistochemistry tests demonstrated almost complete parenchymal replacement with metastatic SCLC. The patient was considered to be too unwell to receive chemotherapy and hence received best supportive care instead, and died shortly thereafter.

Pleural fluid cell-free DNA integrity index to identify cytologically negative malignant pleural effusions including mesotheliomas.

BACKGROUND: The diagnosis of malignant pleural effusions (MPE) is often clinically challenging, especially if the cytology is negative for malignancy. DNA integrity index has been reported to be a marker of malignancy. The aim of this study was to evaluate the utility of pleural fluid DNA integrity index in the diagnosis of MPE. METHODS: We studied 75 pleural fluid and matched serum samples from consecutive subjects. Pleural fluid and serum ALU DNA repeats [115bp, 247bp and 247bp/115bp ratio (DNA integrity index)] were assessed by real-time quantitative PCR. Pleural fluid and serum mesothelin levels were quantified using ELISA. RESULTS: Based on clinico-pathological evaluation, 52 subjects had MPE (including 16 mesotheliomas) and 23 had benign effusions. Pleural fluid DNA integrity index was higher in MPE compared with benign effusions (1.2 vs. 0.8; p<0.001). Cytology had a sensitivity of 55% in diagnosing MPE. If cytology and pleural fluid DNA integrity index were considered together, they exhibited 81% sensitivity and 87% specificity in distinguishing benign and malignant effusions. In cytology-negative pleural effusions (35 MPE and 28 benign effusions), elevated pleural fluid DNA integrity index had an 81% positive predictive value in detecting MPEs. In the detection of mesothelioma, at a specificity of 90%, pleural fluid DNA integrity index had similar sensitivity to pleural fluid and serum mesothelin (75% each respectively). CONCLUSION: Pleural fluid DNA integrity index is a promising diagnostic biomarker for identification of MPEs, including mesothelioma. This biomarker may be particularly useful in cases of MPE where pleural aspirate cytology is negative, and could guide the decision to undertake more invasive definitive testing. A prospective validation study is being undertaken to validate our findings and test the clinical utility of this biomarker for altering clinical practice.

Whole genome sequencing for lung cancer.

Lung cancer is a leading cause of cancer related morbidity and mortality globally, and carries a dismal prognosis. Improved understanding of the biology of cancer is required to improve patient outcomes. Next-generation sequencing (NGS) is a powerful tool for whole genome characterisation, enabling comprehensive examination of somatic mutations that drive oncogenesis. Most NGS methods are based on polymerase chain reaction (PCR) amplification of platform-specific DNA fragment libraries, which are then sequenced. These techniques are well suited to high-throughput sequencing and are able to detect the full spectrum of genomic changes present in cancer. However, they require considerable investments in time, laboratory infrastructure, computational analysis and bioinformatic support. Next-generation sequencing has been applied to studies of the whole genome, exome, transcriptome and epigenome, and is changing the paradigm of lung cancer research and patient care. The results of this new technology will transform current knowledge of oncogenic pathways and provide molecular targets of use in the diagnosis and treatment of cancer. Somatic mutations in lung cancer have already been identified by NGS, and large scale genomic studies are underway. Personalised treatment strategies will improve care for those likely to benefit from available therapies, while sparing others the expense and morbidity of futile intervention. Organisational, computational and bioinformatic challenges of NGS are driving technological advances as well as raising ethical issues relating to informed consent and data release. Differentiation between driver and passenger mutations requires careful interpretation of sequencing data. Challenges in the interpretation of results arise from the types of specimens used for DNA extraction, sample processing techniques and tumour content. Tumour heterogeneity can reduce power to detect mutations implicated in oncogenesis. Next-generation sequencing will facilitate investigation of the biological and clinical implications of such variation. These techniques can now be applied to single cells and free circulating DNA, and possibly in the future to DNA obtained from body fluids and from subpopulations of tumour. As costs reduce, and speed and processing accuracy increase, NGS technology will become increasingly accessible to researchers and clinicians, with the ultimate goal of improving the care of patients with lung cancer.

Array-comparative genomic hybridization reveals loss of SOCS6 is associated with poor prognosis in primary lung squamous cell carcinoma.

BACKGROUND: Primary tumor recurrence commonly occurs after surgical resection of lung squamous cell carcinoma (SCC). Little is known about the genes driving SCC recurrence. METHODS: We used array comparative genomic hybridization (aCGH) to identify genes affected by copy number alterations that may be involved in SCC recurrence. Training and test sets of resected primary lung SCC were assembled. aCGH was used to determine genomic copy number in a training set of 62 primary lung SCCs (28 with recurrence and 34 with no evidence of recurrence) and the altered copy number of candidate genes was confirmed by quantitative PCR (qPCR). An independent test set of 72 primary lung SCCs (20 with recurrence and 52 with no evidence of recurrence) was used for biological validation. mRNA expression of candidate genes was studied using qRT-PCR. Candidate gene promoter methylation was evaluated using methylation microarrays and Sequenom EpiTYPER analysis. RESULTS: 18q22.3 loss was identified by aCGH as being significantly associated with recurrence (p = 0.038). Seven genes within 18q22.3 had aCGH copy number loss associated with recurrence but only SOCS6 copy number was both technically replicated by qPCR and biologically validated in the test set. SOCS6 copy number loss correlated with reduced mRNA expression in the study samples and in the samples with copy number loss, there was a trend for increased methylation, albeit non-significant. Overall survival was significantly poorer in patients with SOCS6 loss compared to patients without SOCS6 loss in both the training (30 vs. 43 months, p = 0.023) and test set (27 vs. 43 months, p = 0.010). CONCLUSION: Reduced copy number and mRNA expression of SOCS6 are associated with disease recurrence in primary lung SCC and may be useful prognostic biomarkers.