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International audience; Inorganic antigens may contribute to paediatric sarcoidosis. Thirty-six patients matched with 36 healthy controls as well as a group of 21 sickle-cell disease (SCD) controls answered an environmental questionnaire. Patients' indirect exposure to inorganic particles, through coresidents' occupations, was higher than in healthy and SCD controls (median score: 2.5 (0.5-7) vs 0.5 (0-2), p=0.003 and 1 (0-2), p=0.012, respectively), especially for construction, exposures to metal dust, talc, abrasive reagents and scouring products. Wood or fossil energies heating were also linked to paediatric sarcoidosis. This study supports a link between mineral environmental exposure due to adult coresident occupations and paediatric sarcoidosis.

BackgroundMacrophages are pivotal cells in sarcoidosis. Monocytes-derived (MD) macrophages have recently been demonstrated to play a major role especially in pulmonary sarcoidosis. From inflammatory tissues to granulomas, they may be exposed to low oxygen tension environments. As hypoxia impact on sarcoidosis immune cells has never been addressed, we designed the present study to investigate MD-macrophages from sarcoidosis patients in this context. We hypothesized that hypoxia may induce functional changes on MD-macrophages which could have a potential impact on the course of sarcoidosis.MethodsWe studied MD-macrophages, from high active sarcoidosis (AS) (n=26), low active or inactive sarcoidosis (IS) (n=24) and healthy controls (n=34) exposed 24 hours to normoxia (21% O2) or hypoxia (1.5% O2). Different macrophage functions were explored: hypoxia-inducible factor-1α (HIF-1α) and nuclear factor-kappa B (NF-κB) activation, cytokines secretion, phagocytosis, CD80/CD86/HLA-DR expression, profibrotic response.ResultsWe observed that hypoxia, with a significantly more pronounced effect in AS compared with controls and IS, increased the HIF-1α trans-activity, promoted a proinflammatory response (TNFα, IL1ß) without activating NF-κB pathway and a profibrotic response (TGFß1, PDGF-BB) with PAI-1 secretion associated with human lung fibroblast migration inhibition. These results were confirmed by immunodetection of HIF-1α and PAI-1 in granulomas observed in pulmonary biopsies from patients with sarcoidosis. Hypoxia also decreased the expression of CD80/CD86 and HLA-DR on MD-macrophages in the three groups while it did not impair phagocytosis and the expression of CD36 expression on cells in AS and IS at variance with controls.ConclusionsHypoxia had a significant impact on MD-macrophages from sarcoidosis patients, with the strongest effect seen in patients with high active disease. Therefore, hypoxia could play a significant role in sarcoidosis pathogenesis by increasing the macrophage proinflammatory response, maintaining phagocytosis and reducing antigen presentation, leading to a deficient T cell response. In addition, hypoxia could favor fibrosis by promoting profibrotic cytokines response and by sequestering fibroblasts in the vicinity of granulomas.

Extrapulmonary sarcoidosis occurs in 30-50% of cases of sarcoidosis, most often in association with pulmonary involvement, and virtually any organ can be involved. Its incidence depends according to the organs considered, clinical phenotype, and history of sarcoidosis, but also on epidemiological factors like age, sex, geographic ancestry, and socio-professional factors. The presentation, symptomatology, organ dysfunction, severity, and lethal risk vary from and to patient even at the level of the same organ. The presentation may be specific or not, and its occurrence is at variable times in the history of sarcoidosis from initial to delayed. There are schematically two types of presentation, one when pulmonary sarcoidosis is first discovered, the problem is then to detect extrapulmonary localizations and to assess their link with sarcoidosis, while the other presentation is when extrapulmonary manifestations are indicative of the disease with the need to promptly make the diagnosis of sarcoidosis. To improve diagnosis accuracy, extrapulmonary manifestations need to be known and a medical strategy is warranted to avoid both under- and over-diagnosis. An accurate estimation of impairment and risk linked to extrapulmonary sarcoidosis is essential to offer the best treatment. Most frequent extrapulmonary localizations are skin lesions, arthritis, uveitis, peripheral lymphadenopathy, and hepatic involvement. Potentially severe involvement may stem from the heart, nervous system, kidney, eye and larynx. There is a lack of randomized trials to support recommendations which are often derived from what is known for lung sarcoidosis and from the natural history of the disease at the level of the respective organ. The treatment needs to be holistic and personalized, taking into account not only extrapulmonary localizations but also lung involvement, parasarcoidosis syndrome if any, symptoms, quality of life, medical history, drugs contra-indications, and potential adverse events and patient preferences. The treatment is based on the use of anti-sarcoidosis drugs, on treatments related to organ dysfunction and supportive treatments. Multidisciplinary discussions and referral to sarcoidosis centers of excellence may be helpful for difficult diagnosis and treatment decisions.

To describe the current knowledge on indications for sarcoidosis treatment.Despite the lack of evidence-based recommendations, the sarcoidosis community has adopted the concept of starting systemic anti-inflammatory treatment because of potential danger (risk of severe dysfunction on major organs or death) or unacceptable impaired quality of life (QoL). On the contrary, while QoL and functionality are patients' priorities, few studies have evaluated treatment effect on patient-reported outcomes. The awareness of long-term corticosteroids toxicities and consequences on QoL and the emergence of novel drugs have changed therapeutic management. Second-line therapy, mainly methotrexate and azathioprine, are indicated for corticosteroids sparing or corticosteroids-resistant sarcoidosis. TNF-α inhibitors are a useful third-line therapy in chronic refractory disease. In addition to organ-targeted treatment, efforts should also be taken for treating nonorgan-specific symptoms, such as physical training for fatigue, and various disease complications.Clinicians should offer a tailored treatment for each patient and ensure a holistic multidisciplinary approach, including pharmacological and nonpharmacological interventions. Patient-centered communication is critical to drive shared decisions, in particular for the tricky situation of isolated impaired QoL as the unique therapeutic indication. Once treatment is decided, clinicians should define a clear therapeutic plan, including goals and instruments to assess response.

Introduction: Sarcoidosis is a systemic granulomatous disease of unknown etiology mostly affecting lungs and lymph nodes. Previous whole-exome sequencing (WES) studies have shown that autophagy and especially Ras-related C3 botulinum toxin substrate 1 (RAC1) and mammalian target of rapamycin (mTOR) pathways were possibly implicated in sarcoidosis (Pacheco et al. Trends Immunol 2020 Accepted manuscript). Aims: The SARCFAM (familial sarcoidosis) cohort gathered families aggregating sarcoidosis cases. We hypothesized that relevant genes variants in patients with sarcoidosis and uveitis phenotype were also related to autophagy. Methods: A WES study was performed on 20 patients in 6 families out of the SARCFAM cohort compared with 10 internal controls among siblings. 2 genomic subtractions were performed to compare uveitis and sarcoidosis phenotype to sarcoidosis without uveitis phenotype and to healthy controls. Results: 4 of the 20 patients presented uveitis phenotype. In 3 different families, 38, 142 and 104 variants concerning autophagy were found and respectively 12, 40 and 34 were associated with the uveitis clinical phenotype. Most relevant genes were NOD2, UNC93B, NLRP14, UBQLNL and those related to Toll-like receptors (TLR5). All genes were shown to be related to autophagy/mTOR/RAC1 pathways. NLRP14/NOD2 polymorphisms were respectively found to be related to Behcet uveitis and Blau syndrome. These proteins are targets for various environmental antigens (viruses, mycobacteria) suggesting imbrication of genetic predisposition and environmental triggers. Conclusion: Autophagy could be a major key point in the pathophysiology of sarcoidosis and mTOR may represent an interesting target to treat sarcoidosis.

Patients with interstitial lung disease have been considered at high risk of complications of COVID-19 because of their underlying lung disease and use of immunosuppressive agents.1 However, data on COVID-19 in patients with sarcoidosis are scarce.2–4 Several reasons for an increased risk of severe forms of COVID-19 among sarcoidosis patients have been hypothesised: the involvement of the lung in almost 90% of patients with COVID-19, some of whom have reduced pulmonary function and comorbidities such as diabetes or hypertension, which are largely associated with the use of glucocorticosteroids for treating sarcoidosis; and the use of immunosuppressive agents in a subset of these patients.5 Recently, Gyorfi et al 6 described the case of a patient with sarcoidosis who experienced a symptomatic SARS-CoV-2 infection with spontaneous clinical improvement, and a virological relapse after steroids treatment. This case illustrated the fact that immunosuppression with glucocorticoids may induce relapse of COVID-19 in patients with sarcoidosis. However, we lack data on the outcomes of patients with sarcoidosis affected by COVID-19. We retrospectively collected data for all patients with sarcoidosis and SARS-CoV-2 infection seen among 15 French centres between 1 March and 20 May 2020. The inclusion criteria were a sarcoidosis diagnosis based on the American Thoracic Society/European Respiratory Society/World Association for Sarcoidosis and other granulomatous diseases …

Purpose of review Sarcoidosis remains a mysterious disease that presents many challenges both in pathogenetic understanding and in the management of patients. This review presents experimental models for sarcoidosis developed since 2016 and discusses their strengths and weaknesses and how they have contributed to the understanding and therapeutic approaches in this disease. In addition, future directions are proposed to overcome the limitations of current models. Recent findings New cellular models using infectious antigen as trigger, and transgenic models in mice have recently been developed to study signaling pathways potentially implicated in the pathogenesis of sarcoidosis. Summary No model fully reproduces sarcoidosis, but most of them generate data supporting key concepts and some open up therapeutic perspectives, like mTOR inhibition or IL-1β blocking. However, there are still many limitations to these models, largely related to the complexity of sarcoidosis, which might be overcome with new technologies, such as mathematical modeling.

Sarcoidosis is a systemic, granulomatous, and noninfectious disease of unknown etiology. The clinical heterogeneity of the disease (targeted tissue(s), course of the disease, and therapy response) supports the idea that a multiplicity of trigger antigens may be involved. The pathogenesis of sarcoidosis is not yet completely understood, although in recent years, considerable efforts were put to develop novel experimental research models of sarcoidosis. In particular, sarcoidosis patient cells were used within in vitro 3D models to study their characteristics compared to control patients. Likewise, a series of transgenic mouse models were developed to highlight the role of particular signaling pathways in granuloma formation and persistence. The purpose of this review is to put in perspective the contributions of the most recent models in the understanding of sarcoidosis.

Multiple problems may be encountered during the diagnosis of sarcoidosis: at first diagnose sarcoidosis in an appropriate clinical setting, secondly, identify any manifestation to be linked to sarcoidosis at diagnosis work-up and during evolution; thirdly, recognize "danger" in sarcoidosis and parasarcoidosis syndromes, and finally, diagnose sarcoidosis recovery. Diagnosis is often delayed as presentation may be diverse, non-specific, or atypical. Diagnosis of sarcoidosis is based on three criteria: a compatible presentation; evidence of non-caseating granulomas and exclusion of any alternative diagnosis. However, even when all criteria are fulfilled, the probability of sarcoidosis diagnosis varies from definite to only possible depending upon the presence of more or less characteristic radio-clinical and histopathological findings and on the epidemiological context. Bilateral hilar lymphadenopathy and/or diffuse lung micronodules mainly along lymphatics are the most frequent highly suggestive findings. Evidence of granulomas relies on superficial biopsies of clinically suspected lesion when present or most often by bronchial endoscopy. The diagnosis of sarcoidosis may be difficult in absence of thoracic or skin manifestations and may require the benefit of hindsight before being definitive. Differential diagnoses, mainly tuberculosis, must be considered. The diagnosis of events during evolution relies on serial clinical, pulmonary function, radiographic evaluation and on extrapulmonary manifestations work-up, including electrocardiogram and blood biology. Affected organs need to be related to sarcoidosis using an appropriate diagnostic assessment instrument. To declare the recovery of sarcoidosis, all manifestations must have disappeared spontaneously or after 3-5 years post-treatment without relapse.

Sarcoidosis is a systemic granulomatous disease that can reduce life expectancy mainly due to pulmonary fibrosis resulting from granulomatous inflammation The lack of vascularization within pulmonary granulomas suggests that macrophages localized in the center of these structures are hypoxic. Hypoxia signaling pathways are known to be pro-inflammatory and pro-fibrotic in various pathological conditions. Recent data suggest an involvement of the transcription factor hypoxia-inducible factor (HIF) in the pathogenesis of sarcoidosis. This could represent a new research approach for the understanding and therapeutic management of sarcoidosis.

To study how demographic differences impact disease manifestation of sarcoidosis using the WASOG tool in a large multicentric study.Clinical data regarding 1445 patients with sarcoidosis from 14 clinical sites in 10 countries were prospectively reviewed from Feb 1, 2020 to Sep 30, 2020. Organ involvement was evaluated for the whole group and for subgroups differentiated by sex, race, and age.The median age of the patients at diagnosis was 46 years old; 60.8% of the patients were female. The most commonly involved organ was lung (96%), followed by skin (24%) and eye (22%). Black patients had more multiple organ involvement than White patients (OR = 3.227, 95% CI: 2.243-4.643) and females had more multiple organ involvement than males (OR = 1.238, 95% CI: 1.083-1.415). Black patients had more frequent involvement of neurologic, skin, eye, extra thoracic lymph node, liver and spleen than White and Asian patients. Women were more likely to have eye (OR = 1.522, 95%CI: 1.259-1.838) or skin involvement (OR = 1.369, 95%CI: 1.152-1.628). Men were more likely to have cardiac involvement (OR = 1.326, 95%CI: 1.096-1.605). A total of 262 (18.1%) patients did not receive systemic treatment for sarcoidosis. Therapy was more common in Black patients than in other races.The initial presentation and treatment of sarcoidosis was related to sex, race, and age. Black and female individuals are found to have multiple organ involvement more frequently. Age at diagnosis45, Black patients and multiple organ involvement were independent predictors of treatment.

Most cases of sarcoidosis are mild and self-limited, with a spontaneous cure. However, in some patients, this disease may also be life-threatening, particularly when severe manifestations induce vital organ dysfunction. Sarcoidosis may also severely impair the quality of life through diverse, persistent disabling symptoms. To date, there is no curative treatment for sarcoidosis, but only anti-inflammatory drugs limiting the pathologic impact of sarcoidosis in reducing enhanced immunity reactions, granulomatous formation, and their consequences. Current anti-inflammatory treatments for sarcoidosis include corticosteroids as the first-line treatment; disease-modifying antisarcoid drugs, mainly immunosuppressive and immunomodulatory drugs, as second-line treatment; and finally tumor necrosis factor (TNF) inhibitors, as third-line treatment. Corticosteroids are most effective; they give rapid results, sometimes with serious, incremental adverse effects. A second-line treatment, mainly low-dose methotrexate and azathioprine, is indicated in case of corticosteroid resistance, intolerance, or contraindication or more often as a corticosteroid-sparing agent when a prolonged treatment of more than 10 mg/d equivalent prednisone is expected. TNF inhibitors are considered in severe refractory sarcoidosis. Infliximab has been proven effective. Usually, treatment for sarcoidosis lasts up to 1 year or longer. The usual drug regimen is made of an induction and then a maintenance protocol before a step-by-step decrease and eventual withdrawal. Contraindications may exist. Each therapeutic decision must follow a rigorous diagnostic evaluation to determine the disease impact, its outcome (progression or not), and its response to treatment in the long run. Pharmacogenetics is still in its infancy, but could help develop a more personalized therapy. Non anti-inflammatory treatments, such as implantable cardiac devices, are also useful, particularly for some organs. In the end, persistent disabling symptoms are very frequent and call for an accurate diagnosis, which may be difficult to treat.

Introduction: The diagnosis of sarcoidosis is often delayed because of the reasons is the diverse presentation of sarcoidosis. Recently the Cincinnati team developed a Sarcoidosis Diagnostic Score(SDS) based on a modified WASOG organ assessment instrument (1). The aim of this study was to confirm the diagnostic value of SDS in a large multinational study, including patients with granulomatous lung diseases not due to sarcoidosis. Methods: This study was conducted in two sites in India (Kolkata, Noida), one in US (Cincinnati) and two in Europe (Belgrade, Greater Paris). There were 1341 cases including 567 with biopsy-confirmed sarcoidosis, 173 with other granulomatous disorders and 601 with non-granulomatous lung disorders. SDS biopsy and SDS clinical (without biopsy) scores were calculated. Positive cutpoint values were defined as ≥4 for clinical and ≥7 for SDS biopsy. Results: In the total sarcoidosis and non-sarcoid granulomatous populations, sensitivity and specificity for SDS biopsy were 100% and 28.9% and for SDS clinical 72.3% and 98.6%, respectively. Considering sarcoidosis and non-granulomatous disorders, Sensitivity and specificity in the sarcoid and non-granulomatous populations for SDS biopsy were 100% and 99.2% and for SDS clinical 73.2% and 91.7%, respectively. Conclusion: The SDS system provides a good discrimination between sarcoidosis and other non-granulomatous diseases similar to the previous report (1). For patients with non-sarcoidosis granulomatous disease, the SDS biopsy was not specific. However, patients with SDS clinical scores of ≥4 had a greater than 90% chance of being diagnosed with sarcoidosis. Higher scores were more likely to be sarcoidosis. Reference: 1) Bickett et al.Chest 2018,154(5)1052–60

Sarcoidosis. Sarcoidosis is a rare, systemic granulomatosis disease of unknown cause. In almost all cases sarcoidosis affects the lung and the lymphatic system. Diagnosis and treatment can be difficult because of highly variable clinicals and evolutions presentations. Clinician must track organ dysfunctions that may be life-threatening (pulmonary, cardiac involment) or that impact functional prognosis (neurological, ophthalmic, renal) and qualified as «dangerous». It is important also to evaluate and take care of persistent signs of discomfort, which can severely affect patients' quality of life. The treatment of sarcoidosis is not systematic, but if necessary, corticosteroids, with notable side effects are the first intention treatment. Second- and third-line treatments are immunosuppressants and TNF antagonists, respectively.Sarcoïdose. La sarcoïdose est une maladie rare, de type granulomatose systémique de cause inconnue touchant presque constamment le poumon et le système lymphatique. Le diagnostic et la prise en charge thérapeutique peuvent être difficiles du fait de la diversité de ses présentations cliniques, du retentissement et de l’évolution de la maladie. Les objectifs du clinicien sont de ne pas manquer les formes avec dysfonction d’un organe pouvant mettre en jeu le pronostic vital (atteinte pulmonaire, cardiaque) ou fonctionnel (formes neurologique, ophtalmique, rénale), qualifiées de « dangereuses » mais aussi d’évaluer et prendre en charge les signes d’inconfort persistants, qui peuvent retentir sévèrement sur la qualité de vie des patients. Le traitement de la sarcoïdose n’est pas systématique mais, si nécessaire, les corticoïdes, aux effets indésirables notables, sont à donner en première intention. Les traitements de deuxième et de troisième ligne sont respectivement les immunosuppresseurs et les anti-tumor necrosis factor alpha.

This article reviews a selection of the scientific presentations on interstitial lung disease (ILD)/diffuse parenchymal lung disease (DPLD) that were made at the 2018 European Respiratory Society (ERS) International Congress in Paris. A number of advances in the epidemiology, pathogenesis, diagnosis and treatment of these disorders were presented and discussed by clinicians and researchers. The research topics span over all four groups of ERS Assembly 12: Interstitial Lung Diseases (Group 12.01: Idiopathic interstitial pneumonias; Group 12.02: ILD/DPLD of known origin; Group 12.03: Sarcoidosis and other granulomatous ILD/DPLD; Group 12.04: Rare ILD/DPLD)., A selection of the scientific presentations on interstitial lung disease from the 2018 #ERSCongress in Paris http://ow.ly/LAbD30nmsFs

Sarcoidosis is a granulomatous disease of unknown cause. This proteiform disease is characterized by an almost constant and often predominant lung involvement. The natural history of disease is difficult to predict at presentation. Diagnosis is based on a compatible clinical and radiological presentation and evidence of non-caseating granulomas. Exclusion of alternative diseases is also required according to clinical presentation. Biopsy samples of superficial lesions should be considered before other sites like per-endoscopic bronchial biopsies or endobronchial ultrasound-guided transbronchial needle aspiration. Therapeutic strategy for lung disease has to take into account the possible spontaneous resolution observed in newly diagnosed patients. Corticosteroids are the first choice when a treatment is decided, which concerns half of patients. Second and third line therapy are based respectively on immunosuppressive drugs and anti-TNFα drugs. Sarcoidosis mortality and morbidity are mainly linked to advanced pulmonary sarcoidosis - lung fibrosis, pulmonary hypertension, bronchial stenosis and chronic pulmonary aspergillosis. "Non anti-inflammatory" treatments have to be considered as well. Clinicians have an essential role in treatment indication, end-point targets and evaluation of response to treatment during follow-up and in finding the best benefice to risk balance. Progress made on pharmacogenetics may offer more personalized treatments for the patients.

Sarcoidosis is a systemic disease of unknown cause with very diverse presentation, outcome, severity and need for treatments. While some presentations may be very typical, for many patients, the presentation is nonspecific, with shared associations with other diseases at times being by far more frequent or misleading, which can be a cause of significant delay and often several consultations before a diagnosis of sarcoidosis can be confirmed. This is particularly the case when pulmonary manifestations are in the forefront. The diagnosis relies on three well-known criteria. In clinical practice, these criteria are not easily implemented, particularly by physicians without expertise in sarcoidosis, which can lead to a risk of either under- or over-diagnosis. Qualifying the presentation according to sarcoidosis diagnosis is essential. However, it is often not easy to classify the presentation as typical versus compatible or compatible versus inconsistent. Further investigations are needed before any other hypothesis is to be considered. It is important to detect events and to determine whether or not they are indicative of a flare of sarcoidosis. Eventually, treatment needs to be related to the correct indications. The evaluation of the efficacy and safety of treatments is crucial. To address such issues, we present five emblematic cases that illustrate this.

Background Sarcoidosis is a systemic disease characterized by the formation of immune granulomas in various organs, mainly the lungs and the lymphatic system. Exaggerated granulomatous reaction might be triggered in response to unidentified antigens in individuals with genetic susceptibility. The present study aimed to determine the genetic variants implicated in a familial case of sarcoidosis. Methods Sarcoidosis presentation and history, NOD2 profile, NF-κB and cytokine production in blood monocytes/macrophages were evaluated in individuals from a family with late appearance of sarcoidosis. Results In the present study, we report a case of familial sarcoidosis with typical thoracic sarcoidosis and carrying the NOD2 2722G > C variant. This variant is associated with the presence of three additional SNPs for the IL17RA, KALRN and EPHA2 genes, which discriminate patients expressing the disease from others. Despite a decrease in NF-κB activity, IL-8 and TNF-A mRNA levels were increased at baseline and in stimulated conditions. Conclusions Combination of polymorphisms in the NOD2, IL17RA, EPHA2 and KALRN genes could play a significant role in the development of sarcoidosis by maintaining a chronic pro-inflammatory status in macrophages. Electronic supplementary material The online version of this article (10.1186/s12931-018-0748-5) contains supplementary material, which is available to authorized users.

Purpose of review Sarcoidosis is a disease caused by a complex combination of genetic susceptibility, immune networks and infectious and/or environmental agents. The onset and phenotypic variability of sarcoidosis remain poorly elucidated, not only due to the lack of clearly identified causes, but also because it is widely considered that no reliable model of this disease is available. In this review, we discuss the various models of granulomatous diseases in order to challenge this assertion. Recent findings A large number of models of granulomatous diseases are available, both cellular models used to study the natural history of granulomas and experimental animal models mostly developed in rodents. Summary Although none of the available models fully reproduces sarcoidosis, most of them generate various data supporting key concepts. Selected models with a high level of confidence among those already published may provide various pieces of the sarcoidosis jigsaw puzzle, whereas clinical data can provide other elements. A 'systems biology' approach for modelling may be a way of piecing together the various pieces of the puzzle. Finally, experimental models and a systemic approach should be considered to be tools for preclinical evaluation of the efficacy of drugs prior to testing in clinical trials.

Chronic pulmonary aspergillosis (CPA) complicating sarcoidosis (SA) is associated with high mortality, and there is a lack of clarity regarding the relative contributions of SA or CPA.This was a retrospective single-centre study on CPA-SA.In total, 65 patients (44 men), aged 41.4±13.5 and 48.3±11.9 years at the time of SA and CPA diagnoses, respectively, were included between 1980 and 2015. Of these, 64 had fibrocystic SA, most often advanced, with composite physiological index (CPI) >40 (65% of patients) and pulmonary hypertension (PH) (31%), and 41 patients (63%) were treated for SA (corticosteroids or immunosuppressive drugs). Chronic cavitary pulmonary aspergillosis (CCPA) was the most frequent CPA pattern. Regarding treatment, 55 patients required long-term antifungals, 14 interventional radiology, 11 resection surgery and two transplantation. Nearly half of the patients (27; 41.5%) died (mean age 55.8 years); 73% of the patients achieved 5-year survival and 61% 10-year survival. Death most often resulted from advanced SA and rarely from haemoptysis. CPI, fibrosis extent and PH predicted survival. Comparison with paired healthy controls without CPA did not show any difference in survival, but a higher percentage of patients had high-risk mould exposure.CPA occurs in advanced pulmonary SA. CPA-SA is associated with high mortality due to the underlying advanced SA rather than to the CPA. CPI, fibrosis extent and PH best predict outcome.