Pulmonary alveolar proteinosis: presentation, diagnostic challenges, and management.

Pulmonary alveolar proteinosis is a rare diffuse lung disease; diagnosis and treatment of which is often delayed. We present the case study of a 43-year-old male with a six-month history of worsening breathlessness and non-productive cough referred for specialist respiratory input. Rapid investigations, including high-resolution computed tomography (HRCT) and bronchoalveolar lavage, confirmed the diagnosis of pulmonary alveolar proteinosis. Treatment with whole lung lavage significantly improved pulmonary function and quality of life. We discuss the diagnosis and management of this condition and highlight the importance of early recognition and multidisciplinary teamwork in managing pulmonary alveolar proteinosis.

The detection, assessment and clinical evolution of interstitial lung abnormalities identified through lung cancer screening.

Introduction: Interstitial lung abnormalities (ILAs) are common incidental findings in lung cancer screening; however, their clinical evolution and longer-term outcomes are less clear. The aim of this cohort study was to report 5-year outcomes of individuals with ILAs identified through a lung cancer screening programme. In addition, we compared patient-reported outcome measures (PROMs) in patients with screen-detected ILAs to newly diagnosed interstitial lung disease (ILD) to assess symptoms and health-related quality of life (HRQoL). Methods: Individuals with screen-detected ILAs were identified, and 5-year outcomes, including ILD diagnoses, progression-free survival and mortality, were recorded. Risk factors associated with ILD diagnosis were assessed using logistic regression and survival using Cox proportional hazard analysis. PROMs were compared between a subset of patients with ILAs and a group of ILD patients. Results: 1384 individuals underwent baseline low-dose computed tomography screening, with 54 (3.9%) identified as having ILAs. 22 (40.7%) were subsequently diagnosed with ILD. 14 (25.9%) individuals died, and 28 (53.8%) suffered disease progression within 5 years. Fibrotic ILA was an independent risk factor for ILD diagnosis, mortality and reduced progression-free survival. Patients with ILAs had lower symptom burden and better HRQoL in comparison to the ILD group. Breathlessness visual analogue scale (VAS) score was associated with mortality on multivariate analysis. Conclusions: Fibrotic ILA was a significant risk factor for adverse outcomes including subsequent ILD diagnosis. While screen-detected ILA patients were less symptomatic, breathlessness VAS score was associated with adverse outcomes. These results could inform risk stratification in ILA.

Pulmonary Sequelae at 4 Months After COVID-19 Infection: A Single-Centre Experience of a COVID Follow-Up Service.

INTRODUCTION: At the end of the first year of the COVID-19 pandemic, more than 78 million known survivors were recorded. The long-term pulmonary sequelae of COVID-19 remain unknown. METHODS: We performed a retrospective analysis of a post-COVID follow-up service to estimate the burden of persistent pulmonary morbidity in hospitalised COVID survivors. RESULTS: A total of 221 patients were followed-up: 44 intensive care unit (ICU) and 177 ward patients. Further investigations were planned as per British Thoracic Society Guidelines: For all ICU patients (n = 44) and for 38 of 177 (21%) ward-based patients who had persistent symptoms and/or persistent radiographic changes on CXR at their initial 8-week follow-up visit. In the ward-based cohort, statistically significant associations with persistent symptoms were being an ex- or current smoker, having pre-existing diabetes, and having a longer length of stay. In patients requiring further investigations, pulmonary function tests (PFTs; n = 67) at an average of 15 weeks post-discharge showed abnormalities in at least one PFT parameter in 79% (equating to 24% of the entire cohort). The most common abnormality was an abnormal diffusion capacity of carbon monoxide (TLCO), highest in the ICU cohort (64% ICU vs. 38% non-ICU). TLCO correlated negatively with length of stay and with maximum inspired FiO2 in the patient group as a whole. In ICU patients, TLCO correlated negatively with maximum inspired positive airway pressure. Computed tomography scans (n = 72) at an average of 18 weeks post-discharge showed evidence of persistent ground glass opacities in 44% and fibrosis in 21% (equating to 7% of the entire cohort). CONCLUSION: Our data add to the growing evidence that there will be pulmonary sequelae in a proportion of COVID survivors, providing some insight into what may become a significant chronic global health problem.

Magnetic Resonance Imaging of Intramyocardial Fat Deposition in Tuberous Sclerosis.

Tuberous sclerosis complex (TSC) is a rare autosomal dominant neurocutaneous syndrome. The phenotype is highly variable and may affect several organ systems, the hallmark of the disease being widespread hamartomas or abnormal growth of normal tissues. Although cardiac rhabdomyomas are the most common cardiac manifestation of TSC, being developed quite early, even during the second semester of the gestation, they tend to regress spontaneously over a period of months or years. On the other hand, the presence of intramyocardial fat deposition has been significantly associated with brain involvement and other extracardiac manifestations. We report the case of a 37-year-old man with TSC who presented to hospital with loss of consciousness, head injury and amnesia and in whom cardiac magnetic resonance imaging revealed the presence of multiple areas intramyocardial fat deposition.

Implementation and outcomes of the RAPID programme: Addressing the front end of the lung cancer pathway in Manchester.

INTRODUCTION: Patients with suspected lung cancer require computed tomography (CT), specialist interpretation of the CT and a consultation with a specialist. Significant time savings could be made with rapid access to these components in the front end of the lung cancer pathway. METHODS: The RAPID programme was launched at Manchester's Wythenshawe Hospital in April 2016. This pathway offers next working day CT for patients with suspected lung cancer, immediate 'hot' reporting of CT images and a same day consultation with a diagnostic specialist. RESULTS: From April 2016 to January 2019, 1,027 patients were referred to the RAPID programme. The median time from referral to CT was 3 days. The CT was hot reported in 94% of patients. The median time from CT to triage and consultation with a diagnostic specialist was 0 days. Overall 56% and 90% of patients had completed a CT and consultation within 3 and 7 days of referral, respectively (0% and 24% prior to implementation). CONCLUSION: Through simple reorganisation of workload, we have significantly reduced the pathway for patients with suspected lung cancer to meet a specialist with a reported CT, something we firmly believe is replicable across all hospitals.

Analysis of lung cancer risk model (PLCOM2012 and LLPv2) performance in a community-based lung cancer screening programme.

INTRODUCTION: Low-dose CT (LDCT) screening of high-risk smokers reduces lung cancer (LC) specific mortality. Determining screening eligibility using individualised risk may improve screening effectiveness and reduce harm. Here, we compare the performance of two risk prediction models (PLCOM2012 and Liverpool Lung Project model (LLPv2)) and National Lung Screening Trial (NLST) eligibility criteria in a community-based screening programme. METHODS: Ever-smokers aged 55-74, from deprived areas of Manchester, were invited to a Lung Health Check (LHC). Individuals at higher risk (PLCOM2012 score ≥1.51%) were offered annual LDCT screening over two rounds. LLPv2 score was calculated but not used for screening selection; ≥2.5% and ≥5% thresholds were used for analysis. RESULTS: PLCOM2012 ≥1.51% selected 56% (n=1429) of LHC attendees for screening. LLPv2 ≥2.5% also selected 56% (n=1430) whereas NLST (47%, n=1188) and LLPv2 ≥5% (33%, n=826) selected fewer. Over two screening rounds 62 individuals were diagnosed with LC; representing 87% (n=62/71) of 6-year incidence predicted by mean PLCOM2012 score (5.0%). 26% (n=16/62) of individuals with LC were not eligible for screening using LLPv2 ≥5%, 18% (n=11/62) with NLST criteria and 7% (n=5/62) with LLPv2 ≥2.5%. NLST eligible Manchester attendees had 2.5 times the LC detection rate than NLST participants after two annual screens (≈4.3% (n=51/1188) vs 1.7% (n=438/26 309); p<0.0001). Adverse measures of health, including airflow obstruction, respiratory symptoms and cardiovascular disease, were positively correlated with LC risk. Coronary artery calcification was predictive of LC (adjOR 2.50, 95% CI 1.11 to 5.64; p=0.028). CONCLUSION: Prospective comparisons of risk prediction tools are required to optimise screening selection in different settings. The PLCOM2012 model may underestimate risk in deprived UK populations; further research focused on model calibration is required.

Spirometry performed as part of the Manchester community-based lung cancer screening programme detects a high prevalence of airflow obstruction in individuals without a prior diagnosis of COPD.

BACKGROUND: COPD is a major cause of morbidity and mortality in populations eligible for lung cancer screening. We investigated the role of spirometry in a community-based lung cancer screening programme. METHODS: Ever smokers, age 55-74, resident in three deprived areas of Manchester were invited to a 'Lung Health Check' (LHC) based in convenient community locations. Spirometry was incorporated into the LHCs alongside lung cancer risk estimation (Prostate, Lung, Colorectal and Ovarian Study Risk Prediction Model, 2012 version (PLCOM2012)), symptom assessment and smoking cessation advice. Those at high risk of lung cancer (PLCOM2012 ≥1.51%) were eligible for annual low-dose CT screening over two screening rounds. Airflow obstruction was defined as FEV1/FVC<0.7. Primary care databases were searched for any prior diagnosis of COPD. RESULTS: 99.4% (n=2525) of LHC attendees successfully performed spirometry; mean age was 64.1±5.5, 51% were women, 35% were current smokers. 37.4% (n=944) had airflow obstruction of which 49.7% (n=469) had no previous diagnosis of COPD. 53.3% of those without a prior diagnosis were symptomatic (n=250/469). After multivariate analysis, the detection of airflow obstruction without a prior COPD diagnosis was associated with male sex (adjOR 1.84, 95% CI 1.37 to 2.47; p<0.0001), younger age (p=0.015), lower smoking duration (p<0.0001), fewer cigarettes per day (p=0.035), higher FEV1/FVC ratio (<0.0001) and being asymptomatic (adjOR 4.19, 95% CI 2.95 to 5.95; p<0.0001). The likelihood of screen detected lung cancer was significantly greater in those with evidence of airflow obstruction who had a previous diagnosis of COPD (adjOR 2.80, 95% CI 1.60 to 8.42; p=0.002). CONCLUSIONS: Incorporating spirometry into a community-based targeted lung cancer screening programme is feasible and identifies a significant number of individuals with airflow obstruction who do not have a prior diagnosis of COPD.

Implementing lung cancer screening: baseline results from a community-based 'Lung Health Check' pilot in deprived areas of Manchester.

We report baseline results of a community-based, targeted, low-dose CT (LDCT) lung cancer screening pilot in deprived areas of Manchester. Ever smokers, aged 55-74 years, were invited to 'lung health checks' (LHCs) next to local shopping centres, with immediate access to LDCT for those at high risk (6-year risk ≥1.51%, PLCOM2012 calculator). 75% of attendees (n=1893/2541) were ranked in the lowest deprivation quintile; 56% were high risk and of 1384 individuals screened, 3% (95% CI 2.3% to 4.1%) had lung cancer (80% early stage) of whom 65% had surgical resection. Taking lung cancer screening into communities, with an LHC approach, is effective and engages populations in deprived areas.

Second round results from the Manchester 'Lung Health Check' community-based targeted lung cancer screening pilot.

We report results from the second annual screening round (T1) of Manchester's 'Lung Health Check' pilot of community-based lung cancer screening in deprived areas (undertaken June to August 2017). Screening adherence was 90% (n=1194/1323): 92% of CT scans were classified negative, 6% indeterminate and 2.5% positive; there were no interval cancers. Lung cancer incidence was 1.6% (n=19), 79% stage I, treatments included surgery (42%, n=9), stereotactic ablative radiotherapy (26%, n=5) and radical radiotherapy (5%, n=1). False-positive rate was 34.5% (n=10/29), representing 0.8% of T1 participants (n=10/1194). Targeted community-based lung cancer screening promotes high screening adherence and detects high rates of early stage lung cancer.

A Review of the Multidisciplinary Diagnosis of Interstitial Lung Diseases: A Retrospective Analysis in a Single UK Specialist Centre.

The accurate diagnosis and management of individuals with interstitial lung diseases (ILDs) poses an interesting challenge in clinical practice. A multidisciplinary team (MDT) approach is considered the gold standard. This is a single-centre retrospective review spanning a five-year period. We assessed the accuracy of prior ILD diagnosis, the methodology used to establish a correct diagnosis and how an MDT approach affected subsequent management. Our data supports an MDT approach in an experienced specialist ILD centre. We have demonstrated that diagnosis is often changed after an MDT review and that this impacts the subsequent management. Our results demonstrate that an MDT approach to diagnosis can establish a diagnosis in the majority of cases when prior diagnosis is uncertain (76%). We also show that a prior diagnosis of idiopathic pulmonary fibrosis is deemed inaccurate in over 50% of cases after MDT discussion. We have shown that during diagnostic uncertainty the considered gold standard of proceeding to a lung biopsy is not always feasible due to disease severity and comorbidities. In these circumstances, an MDT approach to diagnosis of ILDs combines clinical data with serial lung function and disease behavior, with or without responses to previous treatment trials to establish an accurate expert diagnosis.

Development of chronic pulmonary aspergillosis in adult asthmatics with ABPA.

BACKGROUND: Chronic pulmonary aspergillosis (CPA) is an occasional complication of allergic bronchopulmonaryaspergillosis (ABPA) but the transition is poorly understood. METHODS: All patients referred to the UK's National Aspergillosis Centre with CPA between May 2009 and June 2012 were screened with serum total IgE and anti-Aspergillus IgE for a dual diagnosis of ABPA and CPA. Those patients suspected of having both conditions were re-evaluated and their imaging reviewed. RESULTS: Of 407 referred patients, 42 screened positive and 22 were confirmed as having both ABPA and CPA. Asthma was present from early childhood in 19 (86%), the median interval between ABPA and onset of CPA was 7.5 years; one patient developed ABPA and CPA simultaneously. Aspergillus IgG levels varied from 23 to 771 mg/L, median 82 mg/L. All 22 patients had bronchiectasis. In patients with ABPA, CT typically demonstrated varicose or cystic bronchiectasis primarily affecting segmental and proximal subsegmental upper lobe bronchi. Other findings included mucoid impaction and centrilobular nodules. Radiological changes associated with CPA included pleural thickening which was often bilateral and accentuated by adjacent hypertrophied extrapleural fat, upper lobe volume loss, thick walled apical cavities, some of which contained aspergillomas, and cavitating pulmonary nodules. CPA secondary to ABPA has more subtle radiological appearances than when due to other underlying diseases. CONCLUSIONS: CPA may complicate ABPA and have distinct radiology features, in addition to bronchiectasis. A novel biomarker is required to anticipate this serious complication, as current serology is not specific enough.

Incidental extra-cardiac findings on clinical CMR.

AIMS: Cardiac magnetic resonance (CMR) imaging benefits from a large field of view, but consequently captures incidental extra-cardiac findings (IEFs). There is a relative paucity of data for CMR in this regard. Our objectives were to assess the frequency and significance of IEFs reported from clinically indicated CMR scans, and additionally to ascertain if reporting rates differed between radiologist and cardiologist in a 'real-world' setting. METHODS AND RESULTS: A total of 714 patients were included for the study. All patients were referred to a single tertiary cardiac unit for clinically indicated scans. The clinical reports were retrospectively reviewed for reported IEF, and classified as 'minor', or 'major' depending on the need of further investigation or clinical correlation. A total of 180 IEFs were reported in 154 (21.6%) patients. Ninety IEFs were considered minor, and 90 major. Of the latter, eight (1.1%) were considered highly significant. Two hundred scans were reported by a consultant radiologist, and 514 by cardiologists. There was no significant difference in the rates of IEF reporting between the two specialties (P = 0.38). CONCLUSION: IEFs are common, requiring further investigation in a substantial minority. The incidence of highly significant findings in this study was low (∼1%), and similar to the reported incidence in the computed tomography literature. No significant difference was found between the reporting rates of IEFs between different specialties.