Management strategies for pulmonary sarcoidosis

Sarcoidosis is a systemic inflammatory condition with an unexplained predilection for the lung: over 90% of patients have radiographic or physiological abnormalities. Respiratory physicians therefore often manage patients, but any organ may be involved, with noncaseating granulomas the characteristic feature. Sarcoidosis is the commonest interstitial lung disease (ILD), differing from most other ILDs in that many patients remain asymptomatic or improve spontaneously. Careful baseline assessment of disease distribution and severity is thus central to initial management. Subsequently, the unpredictable clinical course necessitates regular monitoring. Sarcoidosis occurs worldwide, with a high prevalence in Afro-Caribbeans and those of Swedish or Danish origin. African Americans also tend to have severe disease. Oral corticosteroids have been used since the 1950s, with evidence of short to medium response; more recent studies have examined the role of inhaled steroids. Long-term benefits of steroids remain uncertain. International guidelines published in 1999 represent a consensus view endorsed by North American and European respiratory societies. Updated British guidelines on interstitial lung disease, including sarcoidosis, were published in 2008. This review describes current management strategies for pulmonary disease, including oral and inhaled steroids, commonly used alternative immunosuppressant agents, and lung transplantation. Tumor necrosis factor alpha inhibitors are briefly discussed

Historical database cohort study addressing the clinical patterns prior to idiopathic pulmonary fibrosis (IPF) diagnosis in UK primary care

OBJECTIVE: To explore the clinical pathways, including signs and symptoms, and symptom progression patterns preceding idiopathic pulmonary fibrosis (IPF) diagnosis. DESIGN AND SETTING: A historical cohort study was conducted using primary care patient records from the Optimum Patient Care Research Database. PARTICIPANTS: Patients included were at least 30 years, had IPF diagnosis, identified via clinical-coding and free-text records and had a consultation with a chest specialist prior to IPF diagnosis. OUTCOME MEASURES: The signs and symptoms in the year prior to IPF diagnosis from clinical codes and free-text in primary care electronic records included: cough, dyspnoea, dry cough, weight loss, fatigue/malaise, loss of appetite, crackles and clubbed fingers. The time course of presentations of clinical features and investigations in the years prior to IPF diagnosis were mapped. RESULTS: Within 462 patients identified, the majority (77.9%) had a respiratory consultation within 365 days prior to the chest specialist visit preceding the IPF diagnosis recorded in their primary care records. The most common symptoms recorded in the 1 year prior to IPF diagnosis were dyspnoea (48.7%) and cough (40.9%); other signs and symptoms were rarely recorded (<5%). The majority of patients with cough (58.0%) and dyspnoea (55.0%) in the 1 year before IPF diagnosis had multiple recordings of the respective symptoms. Both cough and dyspnoea were recorded in 23.4% of patients in the year prior to diagnosis. Consultation rates for cough, dyspnoea and both, but not other signs or symptoms, began to increase 4 to 5 years prior diagnosis, with the sharpest increase in the last year. Cough and dyspnoea were often preceded by a reduction in measured weight over 5 years leading to IPF diagnosis. CONCLUSION: Prolonged cough and/or progressive dyspnoea, especially if accompanied with weight loss, should signal for a referral to specialist assessment at the earliest opportunity

Is there a uniform approach to the management of diffuse parenchymal lung disease (DPLD) in the UK? A national benchmarking exercise

BACKGROUND: Benchmarking is the comparison of a process to the work or results of others. We conducted a national benchmarking exercise to determine how UK pulmonologists manage common clinical scenarios in diffuse parenchymal lung disease (DPLD), and to determine current use and availability of investigative resources. We compared management decisions to existing international guidelines. METHODS: Consultant members of the British Thoracic Society were mailed a questionnaire seeking their views on the management of three common scenarios in DPLD. They were asked to choose from various management options for each case. Information was also obtained from the respondents on time served as a consultant, type of institution in which they worked and the availability of a local radiologist and histopathologist with an interest/expertise in thoracic medicine. RESULTS: 370 out of 689 consultants replied (54% response rate). There were many differences in the approach to the management of all three cases. Given a scenario of relapsing pulmonary sarcoidosis in a lady with multiple co-morbidities, half of respondents would institute treatment with a variety of immunosuppressants while a half would simply observe. 42% would refer a 57-year old lady with new onset DPLD for a surgical lung biopsy, while a similar number would not. 80% would have referred her for transplantation, but a fifth would not. 50% of consultants from district general hospitals would have opted for a surgical biopsy compared to 24% from cardiothoracic centres: this may reflect greater availability of a radiologist with special interest in thoracic imaging in cardiothoracic centres, obviating the need for tissue diagnosis. Faced with an elderly male with high resolution CT thorax (HRCT) evidence of usual interstitial pneumonia (UIP), three quarters would observe, while a quarter would start immunosuppressants. 11% would refer for a surgical biopsy. 14% of UK pulmonologists responding to the survey revealed they had no access to a radiologist with an interest in thoracic radiology. CONCLUSION: From our survey, it appears there is a lack of consensus in the management of DPLD. This may reflect lack of evidence, lack of resources or a failure to implement current guidelines

Outcome of Hospitalization for COVID-19 in Patients with Interstitial Lung Disease. An International Multicenter Study.

Rationale: The impact of coronavirus disease (COVID-19) on patients with interstitial lung disease (ILD) has not been established.Objectives: To assess outcomes in patients with ILD hospitalized for COVID-19 versus those without ILD in a contemporaneous age-, sex-, and comorbidity-matched population.Methods: An international multicenter audit of patients with a prior diagnosis of ILD admitted to the hospital with COVID-19 between March 1 and May 1, 2020, was undertaken and compared with patients without ILD, obtained from the ISARIC4C (International Severe Acute Respiratory and Emerging Infection Consortium Coronavirus Clinical Characterisation Consortium) cohort, admitted with COVID-19 over the same period. The primary outcome was survival. Secondary analysis distinguished idiopathic pulmonary fibrosis from non-idiopathic pulmonary fibrosis ILD and used lung function to determine the greatest risks of death.Measurements and Main Results: Data from 349 patients with ILD across Europe were included, of whom 161 were admitted to the hospital with laboratory or clinical evidence of COVID-19 and eligible for propensity score matching. Overall mortality was 49% (79/161) in patients with ILD with COVID-19. After matching, patients with ILD with COVID-19 had significantly poorer survival (hazard ratio [HR], 1.60; confidence interval, 1.17-2.18; P = 0.003) than age-, sex-, and comorbidity-matched controls without ILD. Patients with an FVC of <80% had an increased risk of death versus patients with FVC ≥80% (HR, 1.72; 1.05-2.83). Furthermore, obese patients with ILD had an elevated risk of death (HR, 2.27; 1.39-3.71).Conclusions: Patients with ILD are at increased risk of death from COVID-19, particularly those with poor lung function and obesity. Stringent precautions should be taken to avoid COVID-19 in patients with ILD

Real-world experience of nintedanib for progressive fibrosing interstitial lung disease in the UK

Background Nintedanib slows progression of lung function decline in patients with progressive fibrosing (PF) interstitial lung disease (ILD) and was recommended for this indication within the United Kingdom (UK) National Health Service in Scotland in June 2021 and in England, Wales and Northern Ireland in November 2021. To date, there has been no national evaluation of the use of nintedanib for PF-ILD in a real-world setting.Methods 26 UK centres were invited to take part in a national service evaluation between 17 November 2021 and 30 September 2022. Summary data regarding underlying diagnosis, pulmonary function tests, diagnostic criteria, radiological appearance, concurrent immunosuppressive therapy and drug tolerability were collected via electronic survey.Results 24 UK prescribing centres responded to the service evaluation invitation. Between 17 November 2021 and 30 September 2022, 1120 patients received a multidisciplinary team recommendation to commence nintedanib for PF-ILD. The most common underlying diagnoses were hypersensitivity pneumonitis (298 out of 1120, 26.6%), connective tissue disease associated ILD (197 out of 1120, 17.6%), rheumatoid arthritis associated ILD (180 out of 1120, 16.0%), idiopathic nonspecific interstitial pneumonia (125 out of 1120, 11.1%) and unclassifiable ILD (100 out of 1120, 8.9%). Of these, 54.4% (609 out of 1120) were receiving concomitant corticosteroids, 355 (31.7%) out of 1120 were receiving concomitant mycophenolate mofetil and 340 (30.3%) out of 1120 were receiving another immunosuppressive/modulatory therapy. Radiological progression of ILD combined with worsening respiratory symptoms was the most common reason for the diagnosis of PF-ILD.Conclusion We have demonstrated the use of nintedanib for the treatment of PF-ILD across a broad range of underlying conditions. Nintedanib is frequently co-prescribed alongside immunosuppressive and immunomodulatory therapy. The use of nintedanib for the treatment of PF-ILD has demonstrated acceptable tolerability in a real-world setting

Role of transforming growth factor β isoforms in the pathogenesis of pulmonary fibrosis

Pulmonary fibrosis is a disease of the lung interstitium characterised by excessive deposition of extracellular matrix proteins including collagen. The aetiology is frequently unclear, but the last decade has generated significant advances in our understanding of the pathogenesis. One current hypothesis is that polypeptide mediators, released by resident lung cells and recruited inflammatory cells, stimulate fibroblast replication and increased collagen synthesis. Interstitial collagen deposition then impedes gas exchange. Of the cytokines studied so far, current evidence strongly implicates transforming growth factor B1 (TGFB1). However, it is now known that there are at least five TGFB isoforms, of which TGFB1-3 are found in mammals. The role of TGFB2 and TGFB3 in the pathogenesis of pulmonary fibrosis is currently unclear. The overall aim of this thesis was to examine the role of the three different TGFB isoforms in the pathogenesis of pulmonary fibrosis. In so doing, I addressed the hypothesis that TGFB1, TGFB2 and TGFB3 play distinct but overlapping roles in the pathogenesis of this disease. To address this hypothesis, the effect of TGFB2 and TGFB3 on human lung fibroblast procollagen metabolism was examined in vitro, TGFB1-3 all stimulated fibroblast procollagen production. TGFB3 was the most potent and also reduced intracellular procollagen degradation. Secondly, a non-isotopic in situ hybridisation technique was developed for use in lung tissue. This enabled the localisation of TGFB isoform gene expression in normal and fibrotic murine and human lung. TGFB1 and TGFB3 mRNA transcripts were demonstrated in a wide variety of lung cells not hitherto recognised to express these genes, and TGFB3 gene expression was demonstrated in human lung for the first time. TGFB1 but not TGFB3 gene expression was enhanced during bleomycin-induced lung injury in mice, and TGFB1 gene expression was more consistently enhanced in human lung fibrosis than was that of TGFB3. Taken together, these data suggest that TGFB1 is the predominant isoform implicated in the pathogenesis of this disease. Finally, results with the TGFB2 riboprobes yielded positive hybridisation signal using the sense probe, but little or no signal using the antisense probe. These results and further studies involving characterisation of the TGFB2 probes and Northern analysis of rat lung and murine lung cells suggested that a natural TGFB2 antisense transcript is present in mammalian lung

Managing patients with stable respiratory disease planning air travel: a primary care summary of the British Thoracic Society recommendations

Air travel poses medical challenges to passengers with respiratory disease, principally because of exposure to a hypobaric environment. In 2002 the British Thoracic Society published recommendations for adults and children with respiratory disease planning air travel, with a web update in 2004. New full recommendations and a summary were published in 2011, containing key recommendations for the assessment of high-risk patients and identification of those likely to require in-flight supplemental oxygen. This paper highlights the aspects of particular relevance to primary care practitioners with the following key points: (1) At cabin altitudes of 8000 feet (the usual upper limit of in-flight cabin pressure, equivalent to 0.75 atmospheres) the partial pressure of oxygen falls to the equivalent of breathing 15.1% oxygen at sea level. Arterial oxygen tension falls in all passengers; in patients with respiratory disease, altitude may worsen preexisting hypoxaemia. (2) Altitude exposure also influences the volume of any air in cavities, where pressure x volume remain constant (Boyle's law), so that a pneumothorax or closed lung bulla will expand and may cause respiratory distress. Similarly, barotrauma may affect the middle ear or sinuses if these cavities fail to equilibrate. (3) Patients with respiratory disease require clinical assessment and advice before air travel to: (a) optimise usual care; (b) consider contraindications to travel and possible need for in-flight oxygen; (c) consider the need for secondary care referral for further assessment; (d) discuss the risk of venous thromboembolism; and (e) discuss forward planning for the journey