Rheumatoid arthritis related interstitial lung disease - improving outcomes over 25 years: a large multicentre UK study.

OBJECTIVE: This study explores whether the prognosis of interstitial lung disease in rheumatoid arthritis (RA-ILD) has improved over time and assesses the potential influence of drug therapy in a large multicentre UK network. METHODS: We analysed data from 18 UK centres on patients meeting criteria for both RA and ILD diagnosed over a 25-year period. Data included age, disease duration, outcome and cause of death. We compared all cause and respiratory mortality between RA controls and RA-ILD patients, assessing the influence of specific drugs on mortality in four quartiles based on year of diagnosis. RESULTS: A total of 290 RA-ILD patients were identified. All cause (respiratory) mortality was increased at 30% (18%) compared with controls 21% (7%) (P =0.02). Overall, prognosis improved over quartiles with median age at death rising from 63 years to 78 years (P =0.01). No effect on mortality was detected as a result of DMARD use in RA-ILD. Relative risk (RR) of death from any cause was increased among patients who had received anti-TNF therapy [2.09 (1.1-4.0)] P =0.03, while RR was lower in those treated with rituximab [0.52(0.1-2.1)] or mycophenolate [0.65 (0.2-2.0)]. Patients receiving rituximab as their first biologic had longer three (92%), five (82%) and seven year (80%) survival than those whose first biologic was an anti-TNF agent (82%, 76% and 64%, respectively) (P =0.037). DISCUSSION: This large retrospective multicentre study demonstrates survival of patients with RA-ILD has improved. This may relate to the increasing use of specific immunosuppressive and biologic agents.

Cardiac sarcoid or arrhythmogenic right ventricular cardiomyopathy: a role for positron emission tomography (PET)?

We present a case of cardiac sarcoidosis of insidious onset mimicking arrhythmogenic right ventricular cardiomyopathy. Our patient initially presented with systemic sarcoidosis but later developed palpitations. The similarity in clinical presentation and cardiac magnetic resonance findings in both conditions posed a challenge in differentiating between the two in the absence of histological diagnosis. We highlighted the role of positron emission tomography in aiding a diagnosis.

Nodules, nodes and non-functioning macrophages: A risk with ibrutinib therapy.

We describe the case of a 70-year-old never smoker with chronic lymphocytic leukaemia, treated with single agent ibrutinib therapy. Chest imaging noted nodular change and mediastinal lymphadenopathy, which showed avid uptake on positron emission tomography and guided subsequent biopsies (bronchoscopy using endobronchial ultrasound, mediastinoscopy). Despite negative aspergillus blood immunology tests, he was found to have invasive aspergillosis, which is a known risk with ibrutinib therapy. He has since been successfully treated with antifungal therapy.

Alveolar proteinosis with hypersensitivity pneumonitis: a new clinical phenotype.

BACKGROUND AND OBJECTIVE: The aim of the present study was to report the features of five patients with concurrent histopathological features of pulmonary alveolar proteinosis (PAP) and hypersensitivity pneumonitis (HP) and their high-resolution CT (HRCT) appearances. METHODS: Patients with histopathological features of both HP and PAP on surgical lung biopsy referred for tertiary review were retrospectively identified. The pathology and HRCT images were semi-quantitatively scored to evaluate the relative contribution to HP and PAP. RESULTS: Five patients had histopathological features of HP and PAP but had varied HRCT appearances. All had imaging features of PAP to a varying degree with two patients also showing characteristics of HP but three patients had ill-defined thickened interlobular septa, not typical of either disease. CONCLUSIONS: We describe the coexistence of PAP and HP in five patients and discuss possible linkages between these two distinct pathologies.

Pulmonary sarcoidosis: a clinical update

Sarcoidosis remains difficult to diagnose, assess and treat. The last decade has brought significant diagnostic and therapeutic advances in the field of sarcoidosis including endobronchial ultrasound, F-fluorodeoxyglucose positron emission tomography and biologics. In this article we use clinical vignettes to discuss commonly encountered cases to illustrate and explain the application of these, and other advances.

Feather duvet lung.

A 43-year-old non-smoker was referred with a 3-month history of malaise, fatigue and breathlessness. Blood avian precipitins were strongly positive. Lung function testing confirmed a restrictive pattern with impaired gas transfer. A 'ground glass' mosaic pattern was seen on CT imaging, suggestive of hypersensitivity pneumonitis. Although he had no pet birds, on closer questioning he had recently acquired a duvet and pillows containing feathers. His symptoms, chest radiograph and lung function tests improved after removal of all feather bedding, and he was also started on oral corticosteroid therapy. Our case reinforces the importance of taking a meticulous exposure history and asking about domestic bedding in patients with unexplained breathlessness. Prompt recognition and cessation of antigen exposure may prevent the development of irreversible lung fibrosis.

Clinical review: idiopathic pulmonary fibrosis--past, present and future.

Idiopathic pulmonary fibrosis (IPF) is an important, and devastating, interstitial lung disease. It has a median mortality of only 3 years, worse than many cancers, and its incidence continues to rise. In this article, an overview of key developments in our understanding and clinical management of IPF will be provided.

Emergence and spread of a human-transmissible multidrug-resistant nontuberculous mycobacterium.

Lung infections with Mycobacterium abscessus, a species of multidrug-resistant nontuberculous mycobacteria, are emerging as an important global threat to individuals with cystic fibrosis (CF), in whom M. abscessus accelerates inflammatory lung damage, leading to increased morbidity and mortality. Previously, M. abscessus was thought to be independently acquired by susceptible individuals from the environment. However, using whole-genome analysis of a global collection of clinical isolates, we show that the majority of M. abscessus infections are acquired through transmission, potentially via fomites and aerosols, of recently emerged dominant circulating clones that have spread globally. We demonstrate that these clones are associated with worse clinical outcomes, show increased virulence in cell-based and mouse infection models, and thus represent an urgent international infection challenge.

Reasons for and consequences of missed appointments in general practice in the UK: questionnaire survey and prospective review of medical records.

BACKGROUND: Missed appointments are a common occurrence in primary care in the UK, yet little is known about the reasons for them, or the consequences of missing an appointment. This paper aims to determine the reasons for missed appointments and whether patients who miss an appointment subsequently consult their general practitioner (GP). Secondary aims are to compare psychological morbidity, and the previous appointments with GPs between subjects and a comparison group. METHODS: Postal questionnaire survey and prospective medical notes review of adult patients missing an appointment and the comparison group who attended appointments over a three week period in seven general practices in West Yorkshire. RESULTS: Of the 386 who missed appointments 122 (32%) responded. Of the 386 in the comparison group 223 (58%) responded, resulting in 23 case-control matched pairs with complete data collection. Over 40% of individuals who missed an appointment and participated said that they forgot the appointment and a quarter said that they tried very hard to cancel the appointment or that it was at an inconvenient time. A fifth reported family commitments or being too ill to attend. Over 90% of the patients who missed an appointment subsequently consulted within three months and of these nearly 60% consulted for the stated problem that was going to be presented in the missed consultation. The odds of missing an appointment decreased with increasing age and were greater among those who had missed at least one appointment in the previous 12 months. However, estimates for comparisons between those who missed appointments and the comparison group were imprecise due to the low response rate. CONCLUSION: Patients who miss appointments tend to cite practice factors and their own forgetfulness as the main reasons for doing so, and most attend within three months of a missed appointment. This study highlights a number of implications for future research. More work needs to be done to engage people who miss appointments into research in a meaningful way.

Effects of adding either a leukotriene receptor antagonist or low-dose theophylline to a low or medium dose of inhaled corticosteroid in patients with persistent asthma.

STUDY OBJECTIVES: To evaluate the effect of adding zafirlukast or low-dose theophylline to a beclomethasone dipropionate (BDP) extra-fine hydrofluoroalkane aerosol on bronchial hyperresponsiveness as the primary outcome variable. METHODS: Twenty-four patients with mild-to-moderate asthma were studied using a randomized crossover design with the following three treatment blocks: (1) beclomethasone, 100 microg/d, alone for the first 2 weeks followed by 400 microg/d alone for the next 2 weeks; (2) beclomethasone, 100 microg/d, followed by 400 microg/d, with the addition of zafirlukast, 20 mg bid; (3) beclomethasone, 100 microg/d, followed by 400 microg/d, with the addition of theophylline, 200 to 300 mg bid. Measurements were made after 2 and 4 weeks of each treatment and at pretreatment baseline. RESULTS: The mean trough plasma theophylline concentration was 6.7 mg/L, coinciding with the anti-inflammatory target range (ie, 5 to 10 mg/L). The provocative dose of methacholine causing a 20% fall in FEV(1) (as doubling dose difference from baseline) was significantly (p < 0.05) greater with beclomethasone, 100 microg, plus zafirlukast (1.1 doubling dose) but not with beclomethasone, 100 microg, plus theophylline (0.7 doubling dose) compared to beclomethasone, 100 microg alone (0.4 doubling dose), but not compared to beclomethasone, 400 microg alone (1.1 doubling dose). There were also significant (p < 0.05) differences between beclomethasone, 100 microg, plus zafirlukast (but not BDP, 100 microg, plus theophylline) vs beclomethasone, 100 microg, alone in terms of nitric oxide level, midexpiratory phase of forced expiratory flow, and peak expiratory flow. There were no further significant improvements observed with the addition of zafirlukast or theophylline to beclomethasone, 400 microg. CONCLUSIONS: A leukotriene receptor antagonist, but not low-dose theophylline, conferred significant additive anti-inflammatory effects to therapy with a low-dose inhaled corticosteroid but not to that with a medium dose of an inhaled corticosteroid. Thus, optimizing the dose of inhaled corticosteroid as monotherapy would seem to be the logical first step, which is in keeping with current guidelines.

Missed appointments in primary care: questionnaire and focus group study of health professionals.

BACKGROUND: The issue of missed appointments in primary care is important for patients and staff. Little is known about how missed appointments, and the people who miss them, are managed in primary care, or about effective strategies for managing missed appointments. AIMS: To understand the perceptions of primary care staff as to why patients miss appointments, to determine how these perceptions influence their management, and to explore the merit of different management strategies. DESIGN OF STUDY: A postal questionnaire survey and focus group interviews. SETTING: General practices in Yorkshire. RESULTS: Missed appointments were regarded as an important problem. Patient factors rather than practice factors were perceived as most important in causing missed appointments. Intervention strategies appeared to be driven by perceptions of why patients miss appointments. Negative attitudes, embodied in terms such as "offenders" to refer to those who missed appointments were prevalent, and favoured intervention strategies included punishing the patient in some way. Receptionists believed that general practitioners should address the issue of the missed appointment with the patient. General practitioners felt guarded about addressing missed appointments with their patients in case it affected the doctor-patient relationship. CONCLUSION: People who miss appointments were viewed negatively by primary care staff, and most of the reasons for missed appointments were focused on patients. These beliefs underpinned intervention strategies aimed mainly at punishment. Since there is no evidence base concerning interventions that are effective in reducing missed appointments, these negative attitudes may not be beneficial to staff or their patients.

Misdiagnosis of common variable immune deficiency.

We present details of a man who was originally diagnosed with sarcoidosis, based on a combination of nodal granulomatous inflammation and radiology confirming bilateral hilar lymphadenopathy with pulmonary infiltrates. The patient subsequently developed splenomegaly and idiopathic thrombocytopenic purpura (ITP) and, latterly, a severe cavitating pneumonia. Serum immunoglobulins were checked, confirming panhypogammaglobulinaemia, and his diagnosis was revised to common variable immune deficiency (CVID). CVID is a heterogeneous condition, which can mimic sarcoidosis with granulomatous organ involvement and is commonly complicated by autoimmune disorders, including ITP. Prompt recognition is important to allow early introduction of immunoglobulin replacement therapy to decrease infection frequency, reduce development of secondary disease complications and retard progression of tissue damage. Given the potential for misdiagnosis and delay in recognition of CVID, serum immunoglobulin measurement should be a first-line investigation in patients with suspected sarcoidosis, even if the presentation is 'typical'. Current international sarcoidosis guidelines should be revised accordingly.

Causes of pulmonary granulomas: a retrospective study of 500 cases from seven countries.

BACKGROUND: The frequencies of various causes of pulmonary granulomas in pathological material are unknown, as is the influence of geographical location on aetiology. The aim of this study was to identify the causes of pulmonary granulomas in pathological specimens, to define their frequencies, and to determine whether these causes vary by geographical location. METHODS: 500 lung biopsies and resections containing granulomas were reviewed retrospectively by expert pulmonary pathologists from 10 institutions in seven countries. Fifty consecutive cases from each location were assigned a diagnosis based on histological features and available clinical/microbiological data. RESULTS: A specific cause was identified in 58% of cases (290/500), most commonly sarcoidosis (136, 27%) and mycobacterial or fungal infections (125, 25%). Mycobacteria were identified in 19% of cases outside the USA versus 8% within the USA. In contrast, fungi accounted for 19% cases in the USA versus 4% in other locations. Fungi were mostly detected by histology, whereas most mycobacteria were identified in cultures. In 42% of cases (210/500) an aetiology could not be determined. CONCLUSIONS: Across several geographical settings, sarcoidosis and infections are the most common causes of pulmonary granulomas diagnosed in pathological specimens. Fungi are more commonly identified than mycobacteria in the USA, whereas the reverse is true in other countries. A definite aetiology cannot be demonstrated in more than a third of all cases of pulmonary granulomas, even after histological examination. These findings highlight the need to submit material for histology as well as cultures in all cases in which granulomatous disease enters the differential diagnosis.