[Spontaneous pneumothorax: new concepts and current management]. / Pneumothorax spontané: nouveaux concepts et prise en charge actuelle.

Spontaneous pneumothorax is a classical medical condition encountered in emergency centers, and by primary care and respiratory physicians. The traditional distinction between primary and secondary pneumothorax, although old and increasingly blurred, still allows to guide initial management and to determine whether pleurodesis is indicated. In case of spontaneous pneumothorax, a targeted family history is essential because it can suggest the presence of a genetic syndrome as the underlying cause of the pneumothorax, a condition often associated with a high risk of pneumothorax recurrence, and the occurrence of extrathoracic manifestations which may be serious if recognized late. This review addresses the classification of spontaneous pneumothorax, its pathogenesis, the risk factors of occurrence including genetic syndromes, and its management.

Le pneumothorax spontané constitue une situation médicale classique rencontrée dans les centres d'urgence, chez le médecin de premier recours et le pneumologue. La traditionnelle distinction entre pneumothorax primaire et secondaire, bien qu'ancienne et de plus en plus incertaine, permet encore de diriger la prise en charge initiale et de décider si une pleurodèse est indiquée. En cas de pneumothorax spontané, une anamnèse familiale ciblée est primordiale car elle peut suggérer la présence d'un syndrome génétique à l'origine du pneumothorax, souvent associé à un risque élevé de récidive et à la survenue de manifestations extrathoraciques qui peuvent être graves si diagnostiquées tardivement. Cet article aborde la classification du pneumo thorax spontané, sa patho genèse, ses facteurs de risque y compris génétiques, et sa prise en charge.

[Pneumology: what's new in 2022]. / Pneumologie : ce qui a changé en 2022.

This selection of pneumological novelties of the year 2022 is not limited to pharmacological acquisitions but also includes progress in diagnostic strategies and the global management of respiratory diseases. We have chosen three pneumological issues. As cannabis is the most consumed illegal substance in Switzerland, it is important to know its impact on pulmonary physiology. An update of the international guidelines on pulmonary fibrosis as well as the European guidelines on pulmonary hypertension provides practical answers to the many clinical problems encountered in the management of these diseases. The key messages from these two consensus documents are reported here.

Cette sélection de nouveautés pneumologiques de l'année 2022 ne se limite pas aux acquisitions pharmacologiques mais englobe également les progrès obtenus dans les stratégies diagnostiques et la prise en charge globale des affections respiratoires. Notre choix s'est porté sur trois problématiques pneumologiques. Le cannabis étant la substance illégale la plus consommée en Suisse, il est important d'en connaître l'impact sur la physiologie pulmonaire. Une mise à jour des directives internationales sur la fibrose pulmonaire ainsi que celles européennes sur l'hypertension pulmonaire apporte des réponses pratiques aux nombreux problèmes cliniques rencontrés dans la prise en charge de ces maladies. Les messages principaux de ces deux documents de consensus sont rapportés ici.

[Anti-glomerular basement membrane disease]. / Maladie des anticorps anti-membrane basale glomérulaire.

Anti-glomerular basement membrane disease is a rare disease. In its classical presentation it associates rapidly progressive glomerulonephritis and diffuse alveolar hemorrhage, linked to the presence of antibodies targeting type IV collagen in the glomerular and alveolar basal membrane. Anti-GBM disease warrants prompt medical management to limit permanent kidney damage and mortality. Treatment includes plasma exchanges to quickly remove pathogenic antibodies and immunosuppressants to stop their production. This article reviews the pathogenesis and current treatments.

La maladie des anticorps anti-membrane basale glomérulaire (anti-MBG) est une entité rare. Dans sa présentation classique, elle associe une glomérulonéphrite rapidement progressive et une hémorragie alvéolaire diffuse liée à des anticorps dirigés contre le collagène de type IV des membranes basales glomérulaire et alvéolaire. Les pronostics rénal et vital sont engagés. Le traitement doit être prompt et comprend des plasmaphérèses visant à éliminer les anticorps pathogéniques ainsi qu'une immunosuppression destinée à supprimer leur production. Cet article passe en revue la pathogénie et les traitements actuels.

[Short telomere syndrome in adults: a rare entity that should be evoked]. / Syndrome des télomères courts chez l'adulte†: une entité rare qu'il faut savoir évoquer.

Short telomere syndrome (STS) is a group of rare, often underrecognized, diseases caused by defects in telomere-maintenance genes, leading to abnormal telomere shortening and associated with diverse multi-organ manifestations. In pediatric patients, STS typically presents with mucocutaneous or gastrointestinal lesions, bone marrow failure and neoplasia. In adulthood, aplastic bone marrow disease, liver disease and pulmonary fibrosis are classic clinical manifestations. At present, medical treatment options for STS remain limited. Danazol, a synthetic androgenic hormone, can slow down telomere shortening and thus limit the progression of the disease. Finally, hematopoietic, hepatic and pulmonary transplantation, sometimes combined, may be discussed in a multidisciplinary setting in certain situations.

Le syndrome des télomères courts (STC) est un groupe de maladies rares dues à un défaut dans les gènes de maintenance des télomères, provoquant leur raccourcissement anormal et des manifestations cliniques multiorganiques. Dans l'enfance, le STC se présente par des lésions mucocutanées et gastro-intestinales, une insuffisance médullaire et des néoplasies. À l'âge adulte, une atteinte médullaire aplasiante, hépatique, et une fibrose pulmonaire sont des manifestations cliniques classiques. Les options thérapeutiques pour le STC restent limitées. Le danazol, une hormone androgène synthétique, permet, parfois, de freiner le raccourcissement télomérique et de limiter la progression de la maladie. Finalement, les transplantations hématopoïétique, hépatique et pulmonaire sont discutées dans certaines situations de manière multidisciplinaire.

Serum markers of pulmonary epithelial damage in systemic sclerosis-associated interstitial lung disease and disease progression.

BACKGROUND AND OBJECTIVE: The course of systemic sclerosis-associated interstitial lung disease (SSc-ILD) is highly variable, and accurate prognostic markers are needed. KL-6 is a mucin-like glycoprotein (MUC1) expressed by type II pneumocytes, while CYFRA 21-1 is expressed by alveolar and bronchiolar epithelial cells. Both are released into the blood from cell injury. METHODS: Serum KL-6 and CYFRA 21-1 levels were measured in a retrospective (n = 189) and a prospective (n = 118) cohort of SSc patients. Genotyping of MUC1 rs4072037 was performed. Linear mixed-effect models were used to evaluate the relationship with change in lung function parameters over time, while association with survival was evaluated with Cox proportional hazard analysis. RESULTS: In both cohorts, KL-6 and CYFRA 21-1 were highest in patients with lung involvement, and in patients with extensive rather than limited ILD. KL-6 was higher in patients carrying the MUC1 rs4072037 G allele in both cohorts. In patients with SSc-ILD, serum KL-6, but not CYFRA 21-1, was significantly associated with DLCO decline in both cohorts (P = 0.001 and P = 0.004, respectively), and with FVC decline in the retrospective cohort (P = 0.005), but not the prospective cohort. When combining the cohorts and subgrouping by severity (median CPI = 45.97), KL-6 remained predictive of decline in DLCO in both milder (P = 0.007) and more severe disease (P = 0.02) on multivariable analysis correcting for age, gender, ethnicity, smoking history and MUC1 allele carriage. CONCLUSION: Our results suggest serum KL-6 predicts decline in lung function in SSc, suggesting its clinical utility in risk stratification for progressive SSc-ILD.

Immunotherapy-Induced Airway Disease: A New Pattern of Lung Toxicity of Immune Checkpoint Inhibitors.

Immune checkpoint inhibitors (ICIs) have been shown to improve overall and progression-free survival in various cancers but have been associated with various immune-related adverse events (IRAEs), including interstitial lung disease, especially organizing pneumonia. We report 2 cases of isolated severe airway disease attributable to ICIs, a rarely reported pattern of lung toxicity. The first patient received nivolumab with or without ipilimumab in a randomized double-blind trial for locoregional metastatic melanoma. The second patient was treated with nivolumab for lung adenocarcinoma. An IRAE was suspected in both cases due to a temporal relationship between ICI initiation and symptom onset. ICIs were stopped, and high-dose prednisone, inhaled corticosteroids, and bronchodilators were administered, allowing a rapid clinical and functional improvement in Patient 1. In Patient 2, despite prolonged high-dose prednisone, only a stabilization of forced expiratory volume in 1 s could be achieved, and the disease course was complicated by respiratory infections resulting in further loss of lung function. The patient died 1 year later due to progression of metastatic disease. These 2 cases suggest that pulmonary IRAEs secondary to ICIs may present as isolated bronchitis or bronchiolitis, with variable outcomes following ICI withdrawal and systemic corticosteroids.

[Asthma and COPD management during the COVID-19 pandemic]. / Prise en charge de l'asthme et de la BPCO en situation de pandémie de COVID-19.

Numerous patients with asthma or COPD are likely to be infected with SARS-CoV-2 virus. Although data is limited, patients with severe and/or uncontrolled asthma and those with COPD appear to be at increased risk of a more severe course of COVID-19 infection. Usual recommendations for management of asthma and COPD remain valid despite the ongoing epidemic. However, lung function testing and nebulisers should be performed with caution during the COVID-19 pandemic due to a potential risk of virus aerosolisation and contagion during the procedure. Particular care must be taken to identify and protect patients who are particularly vulnerable to COVID-19 infection. Asthma and COPD treatments should be pursued and adapted to ensure optimal control of the lung disease throughout the epidemic, thus reducing the risk of severe COVID-19 disease.

De nombreux patients avec asthme ou BPCO sont susceptibles d'être infectés par le virus SARS-CoV-2. Bien que les données soient encore limitées, les patients souffrant d'un asthme sévère et/ou non contrôlé et ceux avec une BPCO semblent présenter un risque plus élevé d'infection COVID-19 d'évolution sévère. Les recommandations habituelles de prise en charge de l'asthme et de la BPCO restent pour la plupart valables malgré l'épidémie en cours. Cependant, les épreuves fonctionnelles respiratoires et les traitements en nébulisation sont à effectuer avec précaution pendant la pandémie de COVID-19 en raison d'un risque potentiel d'aérosolisation du virus pendant la procédure. Un soin particulier doit être apporté à l'identification et la protection des patients particulièrement vulnérables à l'infection COVID-19. Les traitements de l'asthme et de la BPCO doivent être poursuivis et adaptés dans le but d'assurer un contrôle optimal de la pathologie respiratoire tout au long de l'épidémie et ainsi limiter le risque de maladie COVID-19 grave.

[New developments in systemic sclerosis-associated interstitial lung disease]. / Pneumopathie interstitielle associée à la sclérodermie systémique†: nouveaux développements.

Interstitial lung disease is a frequent complication of systemic sclerosis and has now become the leading cause of death in this disorder. It mainly occurs during the first five years after the diagnosis of systemic sclerosis. Various risk factors are associated with the occurrence of interstitial lung disease, including the presence of anti-topoisomerase I antibodies (Scl-70) and the diffuse cutaneous form of systemic sclerosis. The most common radio-pathological presentation is nonspecific interstitial pneumonia, followed by usual interstitial pneumonia. The classical immunosuppressive treatment of systemic sclerosis-associated interstitial lung disease is evolving, as recent studies suggest a beneficial effect of biological agents such as rituximab and tocilizumab, and antifibrotic drugs such as nintedanib.

La pneumopathie interstitielle est une complication fréquente de la sclérodermie, dont elle est devenue ces dernières années la première cause de mortalité. Elle survient principalement durant les cinq premières années suivant le diagnostic de sclérodermie. Divers facteurs de risque sont associés à sa survenue, dont la présence d'anticorps anti-topoisomérase I (Scl-70) et la forme cutanée diffuse de sclérodermie. La présentation radio-pathologique la plus fréquente est la pneumopathie interstitielle non spécifique, suivie de la pneumopathie interstitielle commune. Le traitement immunosuppresseur classique de la pneumopathie interstitielle associée à la sclérodermie est en évolution, des études récentes suggérant l'efficacité de traitements biologiques comme le rituximab et le tocilizumab, et de médicaments antifibrotiques comme le nintédanib.

[Rheumatoid arthritis-associated interstitial lung disease†: new genetic data and therapeutic perspectives]. / Pneumopathie interstitielle dans la ­polyarthrite rhumatoïde†: nouvelles données génétiques et perspectives thérapeutiques.

Diffuse interstitial lung disease (ILD) is one of the most frequent extra-articular manifestation of rheumatoid arthritis (RA) and is an important factor of morbidity and mortality. However, the physiopathological mechanisms underlying RA-associated ILD remain poorly understood, and disease management is difficult in the absence of effective treatments and international guidelines. The recent identification of genetic variants and mutations similar to those observed in idiopathic pulmonary fibrosis (IPF), a disease affecting exclusively the lung, provides new insights into the understanding of RA-associated ILD. Furthermore, new antifibrotic drugs approved for the treatment of IPF, including pirfenidone and nintedanib, could also prove to be effective for RA-associated ILD. Studies are ongoing to confirm this hypothesis.

La pneumopathie interstitielle diffuse compte parmi les manifestations extra-articulaires les plus fréquentes de la polyarthrite rhumatoïde (PR), et elle est un facteur important de morbidité et de mortalité. Elle reste toutefois mal comprise du point de vue physiopathologique et sa prise en charge est difficile, faute de traitements efficaces et de directives internationales. L'identification récente de variants génétiques et de mutations similaires à ceux observés dans la fibrose pulmonaire idiopathique (FPI), une maladie touchant exclusivement le poumon, offre de nouvelles perspectives de compréhension de la pneumopathie interstitielle associée à la PR. Par ailleurs, les nouveaux traitements antifibrotiques disponibles pour la FPI (pirfénidone et nintédanib) pourraient s'avérer aussi utiles dans la pneumopathie interstitielle associée à la PR. Des études sont en cours pour le déterminer.

Host-Microbial Interactions in Idiopathic Pulmonary Fibrosis.

RATIONALE: Changes in the respiratory microbiome are associated with disease progression in idiopathic pulmonary fibrosis (IPF). The role of the host response to the respiratory microbiome remains unknown. OBJECTIVES: To explore the host-microbial interactions in IPF. METHODS: Sixty patients diagnosed with IPF were prospectively enrolled together with 20 matched control subjects. Subjects underwent bronchoalveolar lavage (BAL), and peripheral whole blood was collected into PAXgene tubes for all subjects at baseline. For subjects with IPF, additional samples were taken at 1, 3, and 6 months and (if alive) 1 year. Gene expression profiles were generated using Affymetrix Human Gene 1.1 ST arrays. MEASUREMENTS AND MAIN RESULTS: By network analysis of gene expression data, we identified two gene modules that strongly associated with a diagnosis of IPF, BAL bacterial burden (determined by 16S quantitative polymerase chain reaction), and specific microbial operational taxonomic units, as well as with lavage and peripheral blood neutrophilia. Genes within these modules that are involved in the host defense response include NLRC4, PGLYRP1, MMP9, and DEFA4. The modules also contain two genes encoding specific antimicrobial peptides (SLPI and CAMP). Many of these particular transcripts were associated with survival and showed longitudinal overexpression in subjects experiencing disease progression, further strengthening the relationship of the transcripts with disease. CONCLUSIONS: Integrated analysis of the host transcriptome and microbial signatures demonstrated an apparent host response to the presence of an altered or more abundant microbiome. These responses remained elevated in longitudinal follow-up, suggesting that the bacterial communities of the lower airways may act as persistent stimuli for repetitive alveolar injury in IPF.

Cystic Lung Disease in Genetic Syndromes with Deficient Tumor Suppressor Gene Function.

Cystic lung diseases constitute a distinct group of rare lung disorders, among which two result from monogenic defects affecting tumor suppressor genes: lymphangioleiomyomatosis, either sporadic or associated with tuberous sclerosis complex, and Birt-Hogg-Dubé syndrome. These disorders have similarities in their clinical expression, including occurrence in young adults, multiple pulmonary cysts, recurrent pneumothorax, skin hamartomas, and renal tumors. However, they markedly differ in their gender distribution, pathogenesis, disease course, and prognosis. Our knowledge on these two rare conditions is rapidly expanding. Management of lymphangioleiomyomatosis has substantially improved in the past decade with the understanding of its pathogenic mechanisms, the discovery of an effective therapy, and development of large cohorts and international guidelines. Birt-Hogg-Dubé syndrome has been described more recently and still awaits deeper understanding of its pathophysiology.

Acute eosinophilic and neutrophilic pneumonia following transarterial chemoembolization with drug-eluting beads loaded with doxorubicin for hepatocellular carcinoma: a case report.

At an intermediate or advanced stage, i.e. stage B or C, based on the Barcelona Clinic Liver Cancer classification of hepatocellular carcinoma (HCC), transarterial chemoembolization (TACE) may be offered as a treatment of palliative intent. We report the case of a patient suffering from acute respiratory distress syndrome after TACE with drug-eluting beads loaded with doxorubicin for HCC. To our knowledge, this is the first case described where a bronchoalveolar lavage was performed, and where significant levels of alveolar eosinophilia and neutrophilia were evident, attributed to a pulmonary toxicity of doxorubicin following liver chemoembolization.

Probability of sporadic lymphangioleiomyomatosis in women presenting with spontaneous pneumothorax.

BACKGROUND: Sporadic lymphangioleiomyomatosis (S-LAM) is a rare low-grade neoplasm of young women characterized by multiple pulmonary cysts leading to progressive dyspnea and recurrent spontaneous pneumothorax (SP). The diagnosis of S-LAM may be delayed by several years. To reduce this delay, chest computed tomography (CT) screening has been proposed to uncover cystic lung disease in women presenting with SP. However, the probability to discover S-LAM in this population has not been determined precisely. The aim of this study was to calculate the probability of finding S-LAM in women presenting with (a) SP, and (b) apparent primary SP (PSP) as first manifestation of S-LAM. METHODS: Calculations were made by applying the Bayes theorem to published epidemiological data on S-LAM, SP and PSP. Each term of the Bayes equation was determined by meta-analysis, and included: (1) the prevalence of S-LAM in the general female population, (2) the incidence rate of SP and PSP in the general female population, and (3) the incidence rate of SP and apparent PSP in women with S-LAM. RESULTS: The prevalence of S-LAM in the general female population was 3.03 per million (95% confidence interval 2.48, 3.62). The incidence rate of SP in the general female population was 9.54 (8.15, 11.17) per 100,000 person-years (p-y). The incidence rate of SP in women with S-LAM was 0.13 (0.08, 0.20). By combining these data in the Bayes theorem, the probability of finding S-LAM in women presenting with SP was 0.0036 (0.0025, 0.0051). For PSP, the incidence rate in the general female population was 2.70 (1.95, 3.74) per 100,000 p-y. The incidence rate of apparent PSP in women with S-LAM was 0.041 (0.030, 0.055). With the Bayes theorem, the probability of finding S-LAM in women presenting with apparent PSP as first disease manifestation was 0.0030 (0.0020, 0.0046). The number of CT scans to perform in women to find one case of S-LAM was 279 for SP and 331 for PSP. CONCLUSION: The probability of discovering S-LAM at chest CT in women presenting with apparent PSP as first disease manifestation was low (0.3%). Recommending chest CT screening in this population should be reconsidered.

Azithromycin alters spatial and temporal dynamics of airway microbiota in idiopathic pulmonary fibrosis.

Background: High bacterial burden in the lung microbiota predicts progression of idiopathic pulmonary fibrosis (IPF). Azithromycin (AZT) is a macrolide antibiotic known to alter the lung microbiota in several chronic pulmonary diseases, and observational studies have shown a positive effect of AZT on mortality and hospitalisation rate in IPF. However, the effect of AZT on the lung microbiota in IPF remains unknown. Methods: We sought to determine the impact of a 3-month course of AZT on the lung microbiota in IPF. We assessed sputum and oropharyngeal swab specimens from 24 adults with IPF included in a randomised controlled crossover trial of oral AZT 500 mg 3 times per week. 16S rRNA gene amplicon sequencing and quantitative PCR (qPCR) were performed to assess bacterial communities. Antibiotic resistance genes (ARGs) were assessed using real-time qPCR. Results: AZT significantly decreased community diversity with a stronger and more persistent effect in the lower airways (sputum). AZT treatment altered the temporal kinetics of the upper (oropharyngeal swab) and lower airway microbiota, increasing community similarity between the two sites for 1 month after macrolide cessation. Patients with an increase in ARG carriage had lower bacterial density and enrichment of the genus Streptococcus. In contrast, patients with more stable ARG carriage had higher bacterial density and enrichment in Prevotella. Conclusions: AZT caused sustained changes in the diversity and composition of the upper and lower airway microbiota in IPF, with effects on the temporal and spatial dynamics between the two sites.

Sarcoidosis - a multisystem disease.

Sarcoidosis is a systemic inflammatory disease, characterised by granuloma formation upon an unknown trigger in genetically predisposed individuals. The inflammation is characterised by an activation of both the innate immune system, with macrophages differentiating into epitheloid cells and dendritic cells, and the adaptive immune system, particularly T helper (Th) 1 and Th17 cells. Since all organs can be affected to varying extents, clinical presentation is often diverse. Most commonly, the lungs, lymph nodes, skin and eyes are involved, whereas cardiac, renal and neurological manifestations are less common but associated with higher morbidity. Depending on the clinical symptoms, a detailed evaluation including thorough clinical examination, imaging and laboratory tests should explore all possible organ involvements. In some patients, fatigue manifests as a para-sarcoidosis symptom impacting quality of life, even if sarcoidosis is in remission. Some acute syndromic presentations, such as Löfgren's syndrome, have a good prognosis and are commonly self-limiting. If possible, a topical treatment, for example for cutaneous sarcoidosis or bronchial involvement, should be applied. Treatment of severe cases with persisting disease activity necessitates long-term immunosuppressive drugs, with glucocorticoids as the first-line option. Steroid-sparing and second-line drugs include methotrexate, azathioprine, mycophenolate mofetil and immunomodulators such hydroxychloroquine, with the latter being first-line therapy in cutaneous sarcoidosis. Tumour necrosis factor-alpha inhibitors (particularly adalimumab and infliximab) are used as third-line agents but are administered earlier in cases of persistent disease activity, severe organ-involvement or intolerance to conventional drugs. Treatment decisions should be based on a multidisciplinary approach, depending on organ involvement and treatment tolerability. Para-sarcoidosis manifestations, particularly fatigue, should also be carefully addressed, where the patient could also be enrolled in multidimensional rehabilitation programmes. With various organ involvement and different phenotypes, larger studies including real-world data from registries are necessary to evaluate different sarcoidosis endotypes and preferential treatment pathways.

Prevalence of Birt-Hogg-Dubé Syndrome Determined Through Epidemiological Data on Spontaneous Pneumothorax and Bayes Theorem.

Background: Birt-Hogg-Dubé syndrome (BHD) is a rare inherited disorder characterized by cutaneous fibrofolliculomas, multiple pulmonary cysts, recurrent spontaneous pneumothorax (SP), and renal tumors. More than 40 years after its description, the prevalence of BHD in the general population remains unknown. This study aimed at determining the prevalence of BHD by applying the Bayes theorem of conditional probability to epidemiological data on SP. Methods: We performed a meta-analysis of published data on: (1) the probability of having BHD among patients with apparent primary SP (4 studies), (2) the incidence rate of primary SP in the general population (9 studies), and (3) the probability of experiencing a SP in BHD (16 studies). Results were corrected for SP relapses, stratified by gender and year of study publication (before and after 2000), and computed with the Bayes equation. Results: The probability of having BHD among patients with apparent primary SP was 0.09 (95% confidence interval: 0.07, 0.11) or 9%. It was 0.20 (0.14, 0.27) in women and 0.05 (0.04, 0.07) in men. The incidence rate of primary SP in the general population was 8.69 (6.58, 11.46) per 100,000 person-years (p-y). It was 3.44 (2.36, 4.99) per 100,000 p-y in women and 13.96 (10.72, 18.18) per 100,000 p-y in men, and was about 2 times higher in studies published after 2000 than in those published before 2000. The probability of experiencing at least one SP among patients with BHD was 0.43 (0.31, 0.54) or 43%, without gender difference. By combining these data in the Bayes equation, we found a prevalence of BHD in the general population of 1.86 (1.16, 3.00) per million, with values of 1.86 (1.02, 3.39) per million in men, and 1.88 (0.97, 3.63) per million in women. Conclusion: The prevalence of BHD in the general population is about 2 cases per million, without difference between genders.

Birt-Hogg-Dubé syndrome.

Birt-Hogg-Dubé syndrome (BHD) is a rare inherited autosomal dominant disorder caused by germline mutations in the tumour suppressor gene FLCN, encoding the protein folliculin. Its clinical expression typically includes multiple pulmonary cysts, recurrent spontaneous pneumothoraces, cutaneous fibrofolliculomas and renal tumours of various histological types. BHD has no sex predilection and tends to manifest in the third or fourth decade of life. Multiple bilateral pulmonary cysts are found on chest computed tomography in >80% of patients and more than half experience one or more episodes of pneumothorax. A family history of pneumothorax is an important clue, which suggests the diagnosis of BHD. Unlike other cystic lung diseases such as lymphangioleiomyomatosis and pulmonary Langerhans cell histiocytosis, BHD does not lead to progressive loss of lung function and chronic respiratory insufficiency. Renal tumours affect about 30% of patients during their lifetime, and can be multiple and recurrent. The diagnosis of BHD is based on a combination of genetic, clinical and/or skin histopathological criteria. Management mainly consists of early pleurodesis in the case of pneumothorax, periodic renal imaging for tumour detection, and diagnostic work-up in search of BHD in relatives of the index patient.

Effect of everolimus on multifocal micronodular pneumocyte hyperplasia in tuberous sclerosis complex.

Multifocal micronodular pneumocyte hyperplasia (MMPH) is a benign proliferation of alveolar type II cells presenting as multiple pulmonary nodules at chest imaging, which is frequently seen in patients with tuberous sclerosis complex (TSC). We report a case of a woman with TSC and MMPH who received everolimus, a mechanistic target of rapamycin (mTOR) inhibitor, for the treatment of a subependymal giant cell astrocytoma (SEGA). After 3 months of therapy, a remarkable decrease in density of all pulmonary MMPH lesions was observed, without any change in size. This shows that everolimus is active on MMPH similarly to its effects on SEGA, renal angiomyolipomas, and pulmonary lymphangioleiomyomatosis in TSC, and suggests that the dysregulated activation of mTOR which characterizes TSC also plays a role in the pathogenesis of MMPH.