Biologics (mepolizumab and omalizumab) induced remission in severe asthma patients.

BACKGROUND: Asthma remission has emerged as a potential treatment goal. This study evaluated the effectiveness of two biologics (mepolizumab/omalizumab) in achieving asthma remission. METHODS: This observational study included 453 severe asthma patients (41% male; mean age ± SD 55.7 ± 14.7 years) from two real-world drug registries: the Australian Mepolizumab Registry and the Australian Xolair Registry. The composite outcome clinical remission was defined as zero exacerbations and zero oral corticosteroids during the previous 6 months assessed at 12 months and 5-item Asthma Control Questionnaire (ACQ-5) ≤1 at 12 months. We also assessed clinical remission plus optimization (post-bronchodilator FEV1 ≥80%) or stabilization (post-bronchodilator FEV1 not greater than 5% decline from baseline) of lung function at 12 months. Sensitivity analyses explored various cut-offs of ACQ-5/FEV1 scores. The predictors of clinical remission were identified. RESULTS: 29.3% (73/249) of AMR and 22.8% (37/162) of AXR cohort met the criteria for clinical remission. When lung function criteria were added, the remission rates were reduced to 25.2% and 19.1%, respectively. Sensitivity analyses identified that the remission rate ranged between 18.1% and 34.9% in the AMR cohort and 10.6% and 27.2% in the AXR cohort. Better lung function, lower body mass index, mild disease and absence of comorbidities such as obesity, depression and osteoporosis predicted the odds of achieving clinical remission. CONCLUSION: Biologic treatment with mepolizumab or omalizumab for severe asthma-induced asthma remission in a subgroup of patients. Remission on treatment may be an achievable treatment target and future studies should consider remission as an outcome measure.

Emergency department management of acute exacerbations of chronic obstructive pulmonary disease and factors associated with hospitalization.

BACKGROUND: Currently there is a paucity of information about biomarkers that can predict hospitalization for acute exacerbations of chronic obstructive pulmonary disease (AECOPD) patients presenting to the emergency department (ED). There is limited data on the consistency of ED management of AECOPD with local COPD guidelines. The aim of this study was to identify biomarkers associated with hospitalization in AECOPD patients and to determine if the ED management was concordant with local COPD guidelines. MATERIALS AND METHODS: We performed a retrospective audit of consecutive AECOPD patients presenting to the Gold Coast Hospital ED over a 6-month period. RESULTS: During the study period, 122 AECOPD patients (51% male, mean age (SE) 71 (±11) years) presented to the ED. Ninety-eight (80%) patients were hospitalized. Univariate analysis identified certain factors associated with hospitalization: Older age, former smokers, home oxygen therapy, weekday presentation, SpO2 < 92%, and raised inflammatory markers (white cell count (WCC) and C-reactive protein (CRP)). After adjustment for multiple variable, increased age was significantly associated with hospitalization (odds ratio (OR) 1.09; 95% confidence interval (CI): 1.00-1.18; P = 0.05). Radiology assessment and pharmacological management was in accordance with COPD guidelines. However, spirometry was performed in 17% of patients and 28% of patients with hypercapneic respiratory failure received noninvasive ventilation (NIV). CONCLUSION: We identified several factors on univariate analysis that were associated with hospitalization. Further research is required to determine the utility of these biomarkers in clinical practice. Also, while overall adherence to local COPD guidelines was good, there is scope for improvement in performing spirometry and provision of NIV to eligible patients.

Artificial intelligence software in pulmonary nodule assessment.

BACKGROUND: This study tests the impact of the addition of autonomous computed tomography (CT) interpreting software to radiologist assessment of pulmonary nodules. METHODS: Computed tomography scans for nodule assessment were identified retrospectively. Lung cancer risk factors, initial radiologist (RAD) report, Philips Lung Nodule software report (computer-aided nodule (CAD)) and radiologist report following the review of CT images and CAD (RAD + CAD) were collected. Follow-up recommendations based on current guidelines were derived from each report. RESULTS: In all, 100 patients were studied. Median maximal diameter of the largest nodule reported by RAD and RAD + CAD were similar at 10.0 and 9.0 mm, respectively (p = 0.06) but were reported as larger by CAD at 11.8 mm (p < 0.001). Follow-up recommendations derived from RAD + CAD were less intensive in 23 (23%) and more intensive in 34 (34%) than that of RAD. DISCUSSION: This study suggests that autonomous software use can alter radiologist assessment of pulmonary nodules such that suggested follow-up is altered.

Mepolizumab and Oral Corticosteroid Stewardship: Data from the Australian Mepolizumab Registry.

BACKGROUND: Oral corticosteroids (OCS) carry serious health risks. Innovative treatment options are required to reduce excessive exposure and promote OCS stewardship. OBJECTIVES: This study evaluated the trajectories of OCS exposure (prednisolone-equivalent) in patients with severe eosinophilic asthma before and after starting mepolizumab and the predictors of becoming OCS free after 6 months of mepolizumab therapy. METHODS: This real-world observational study included 309 patients from the Australian Mepolizumab Registry who were followed up for 1 year (n = 225). RESULTS: Patients had a median age of 60 (interquartile range: 50, 68) years, and 58% were female. At baseline, 48% used maintenance OCS, 96% had ≥1 OCS burst, and 68% had received ≥1 g of OCS in the previous year. After commencing mepolizumab, only 55% of those initially on maintenance OCS remained on this treatment by 12 months. Maintenance OCS dose reduced from median 10 (5.0, 12.5) mg/day at baseline to 2 (0, 7.0) mg/day at 12 months (P < .001). Likewise, proportions of patients receiving OCS bursts in the previous year reduced from 96% at baseline to 50% at 12 months (P < .001). Overall, 137 (48%) patients required OCS (maintenance/burst) after 6 months' mepolizumab therapy. Becoming OCS free was predicted by a lower body mass index (odds ratio: 0.925; 95% confidence interval: 0.872-0.981), late-onset asthma (1.027; 1.006-1.048), a lower Asthma Control Test score (1.111; 0.011-1.220), and not receiving maintenance OCS therapy at baseline (0.095; 0.040-0.227). CONCLUSION: Mepolizumab led to a significant and sustained reduction in OCS dependence in patients with severe eosinophilic asthma. This study supports the OCS-sparing effect of mepolizumab and highlights the pivotal role of mepolizumab in OCS stewardship initiatives.

Pleural effusion in patients with pulmonary embolism.

BACKGROUND AND OBJECTIVE: It has been suggested that pulmonary embolism (PE) is an under-recognized cause of pleural effusion. This study aimed to (i) establish the incidence and clinical relevance of pleural effusion in patients with pulmonary emboli; and (ii) determine if there is a relationship between development of pleural effusions and the location of emboli and number of pulmonary arteries involved. METHODS: A retrospective analysis of all CT pulmonary angiograms (CTPA) performed over 12 months on adult patients with clinically suspected PE in a hospital which used CTPA as first-line imaging investigation for PE. RESULTS: Of 285 CTPA, 60 patients (21%) had evidence of pulmonary emboli (38 had both central and peripheral clots and 22 peripheral emboli only). Emboli were bilateral in 39 cases and unilateral in 21 cases. Pleural effusion was present in almost one half (n = 29, 48%) of the patients with pulmonary emboli. Patients with pulmonary emboli were more likely to have a pleural effusion (OR 2.2 (95% CI: 1.1-4.7), P < 0.05) than patients without PE; however, the effusions were generally very small. Most (86%) of the effusions were present on the same side as the emboli. The location of emboli and number of arteries involved did not predict the presence of pleural effusions. CONCLUSIONS: Pleural effusion is common in patients with pulmonary emboli demonstrated on CTPA. These effusions are small and seldom alter clinical management. Clinicians should therefore have a high threshold of suspicion in attributing large or contralateral pleural effusions to embolic diseases without excluding alternative diagnoses.

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.

Effect of changing from the National Health and Nutritional Examination Survey III spirometry reference range to that of the Global Lung Initiative 2012 at Gold Coast Hospital and Health Service.

The categorisation of lung disease into obstructive ventilatory defect (OVD) and tendency to a restrictive ventilatory defect (TRVD) patterns using spirometry is used to guide both prognostication and treatment. The effectiveness of categorisation depends upon having reference ranges that accurately represent the population they describe. The Global Lung Initiative 2012 (GLI 2012) has spirometry reference ranges drawn from the largest sample size to date. This study aimed to determine whether using spirometry reference ranges from the new GLI 2012 dataset, compared to the previously used National Health and Nutritional Examination Survey III (NHANES III) dataset, resulted in a change in diagnosis between OVD, TRVD and normal ventilatory pattern (NVP). Spirometry data were collected from 301 patients, aged 18-80 years, undergoing investigation at the Gold Coast Hospital and Health Service (GCHHS) throughout February and March 2014. OVD was defined as a forced expiratory volume in 1 second (FEV1) divided by forced vital capacity (FVC) less than lower limit of normal (LLN). TRVD was defined as FEV1/FVC ≥ LLN, FEV1 < LLN, and FVC < LLN. The LLN values were determined by equations from the GLI and NHANES datasets. Spirometry interpreted using the NHANES III equations showed: 102 individuals (33.9%) with normal spirometry, 136 (45.2%) with an OVD pattern, 52 (17.3%) with a TRVD pattern, and 11 (3.7%) with a mixed pattern. When the spirometry data were interpreted using the GLI 2012 equations 2 (0.7%) individuals changed from OVD to NVP, 2 (0.7%) changed from NVP to OVD and 14 (4.7%) changed from TRVD to NVP. Using the GLI 2012 reference range resulted in a change in diagnosis of lung disease in 5.9% of the individuals included in this study. This variance in diagnosis when changing reference ranges should be taken into account by clinicians as it may affect patient management.

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.

Delays in the assessment and management of primary lung cancers in South Auckland.

AIM: To determine the patient characteristics, referral patterns and delays in assessment and treatment of patients with primary lung cancer in South Auckland, New Zealand and compare with international standards. METHODS: Retrospective review of the clinical records of 80 patients referred to a secondary care respiratory service and diagnosed with primary lung cancer in 2004. RESULTS: Eighty-five percent of inpatient referrals and 48.5% of outpatient referrals were for advanced stage lung cancers. The median interval from receipt of outpatient referral to first chest physician assessment was 18 days, with median interval from the first chest physician assessment to bronchoscopy of 17 days and for staging CT chest of 16 days. For patients requiring a CT-guided percutaneous needle aspiration for diagnosis, there was a further median delay of 37 days after the initial CT scan. The median interval from the date of receipt of initial outpatient referral to diagnosis was 38 days, but for early stage lung cancers it was 54 days. The median interval to diagnosis for inpatient admissions was 6 days after the first respiratory assessment. CONCLUSION: The intervals for initial assessment, diagnosis and treatment of lung cancer in South Auckland do not meet the recommendations of international guidelines, especially for early stage lung cancers. Organisational and resource changes are required at each point in the diagnostic and management pathway to reduce delays.

The training, experience, and confidence of junior doctors in performing pleural procedures.

AIM: Pleural procedures may cause patient discomfort and serious complications if performed inadequately. We surveyed junior doctors to provide information about training and experience. METHODS: We surveyed 493 junior doctors working in departments involved in pleural procedures in three teaching hospitals via postal questionnaires in 2002. RESULTS: The response rate was 66%. Formal training in the performance of pleural procedures was limited at undergraduate and postgraduate levels. Theoretical training at postgraduate level in pleural aspiration, chest drain insertion, and closed pleural biopsies was reported by 34%, 40%, and 14% of respondents respectively. Practical training using animal or artificial models occurred infrequently. Pleural aspiration, chest drain insertion, and pleural biopsy had been performed at least once by 91%, 66%, and 41% of respondents respectively. Most doctors felt they needed more training in chest drain insertion and pleural biopsy. Confidence in performing procedures was related to the number of times the procedure had been performed but not to formal teaching. CONCLUSIONS: This study provides a comprehensive survey of the background training, experience and confidence levels of junior medical staff in performing pleural procedures. Training in pleural procedures was limited and our results suggest the need for better training programmes and supervision of junior doctors.

Asbestos-induced and smoking-related disease: apportioning pulmonary function deficit by using thin-section CT.

PURPOSE: To retrospectively correlate the extent of individual diseases seen at thin-section computed tomography (CT) with pulmonary function in an initial group of patients with asbestos-related parenchymal disease (asbestosis) and to test these findings in a subsequent group of patients whose CT scans were retrospectively identified. MATERIALS AND METHODS: This retrospective study had Institutional Review Board approval; informed consent was not required. The study included 133 individuals who had been exposed to asbestos. In the initial study group (81 patients; 79 men, two women; median age, 67 years), two observers used a CT scoring system to quantify the extent of pulmonary fibrosis, diffuse pleural thickening, small-airways disease, and emphysema. Multivariate equations were formulated by using independent CT variables to predict changes in total lung capacity (TLC) and carbon monoxide diffusing capacity (Dlco). The validity of these equations was then tested in a subsequent group of patients (52 patients; all men; median age, 60 years). RESULTS: At thin-section CT, the extent of asbestos-induced pleuropulmonary disease and emphysema correlated significantly with physiologic impairment (P<.001). Combined CT variables predicted 58% and 57% of the variability in TLC and Dlco, respectively, despite considerable variation in the proportion of coexisting pathologic conditions. When predictive equations with CT variables derived from the initial study group were applied to the subsequent study group, predicted TLC (rho=0.75, P<.001) and Dlco (rho=0.64, P<.001) correlated strongly with measured values. CONCLUSION: The proposed CT system provides a semiquantitative method for assessing the relative contribution of asbestos-induced pleuropulmonary disease and smoking-related emphysema to functional impairment.