• Birt-Hogg-Dubé syndrome
• Sjögren disease
• diffuse cystic lung disease
• follicular bronchiolitis
• lymphangioleiomyomatosis
• lymphoid interstitial pneumonia
• pneumothorax
• pulmonary Langerhans cell histiocytosis
• tuberous sclerosis complex

• Humans
• Tomography, X-Ray Computed
• Lung Diseases/diagnosis
• Lung Diseases/therapy
• Birt-Hogg-Dube Syndrome/diagnosis
• Birt-Hogg-Dube Syndrome/therapy
• Lymphangioleiomyomatosis/diagnosis
• Lymphangioleiomyomatosis/therapy
• Histiocytosis, Langerhans-Cell/diagnosis
• Histiocytosis, Langerhans-Cell/therapy
• Lung Diseases, Interstitial/diagnosis
• Lung Diseases, Interstitial/therapy
• Cysts/therapy
• Cysts/diagnosis
• Disease Management
• Diagnosis, Differential

• The French Ministry of Health

• Humans
• Erdheim-Chester Disease/drug therapy
• Histiocytosis, Langerhans-Cell/drug therapy
• Molecular Targeted Therapy/methods
• Adult

• L222081 Beijing Natural Science Haidian frontier Foundation
• 2022-PUMCH-A-193 The National High Level Hospital Clinical Research Funding

• Cigarette smoking
• Desquamative interstitial pneumonia
• Interstitial lung disease
• Smoking
• Smoking-related interstitial fibrosis
• Smoking-related interstitial lung disease

• Humans
• Lung Diseases, Interstitial/pathology
• Lung Diseases, Interstitial/etiology
• Smoking/adverse effects
• Lung/pathology
• History, 20th Century
• History, 21st Century

• Bronchiectasis
• Light chain deposition disease
• Lung cysts
• Lung transplantation

• Humans
• Female
• Young Adult
• Adult
• Male
• Immunoglobulin Light Chains
• Retrospective Studies
• Lung/diagnostic imaging
• Lung/pathology
• Bronchiectasis
• Cysts/pathology
• Phenotype

• Rare lung diseases

• Humans
• Rare Diseases/diagnosis
• Rare Diseases/genetics
• Rare Diseases/complications
• Lung Diseases/etiology
• Lung Diseases, Interstitial/diagnosis
• Cysts/diagnosis
• Cysts/pathology
• United Kingdom
• Diagnosis, Differential

• endophenotype
• histology
• idiopathic pulmonary fibrosis
• pathophysiology
• pulmonary vascular disease

• case report
• cavitary lesion
• nodular change
• pulmonary Langerhans cell histiocytosis
• smoking cessation

• Male
• Humans
• Adult
• Smoking Cessation
• Histiocytosis, Langerhans-Cell/diagnostic imaging
• Histiocytosis, Langerhans-Cell/pathology
• Lung/diagnostic imaging
• Lung/pathology
• Tomography, X-Ray Computed
• Recurrence

• Epidemiology
• Infections
• Late effects
• Long term survival

• Humans
• Lung Diseases, Interstitial/diagnosis
• Lung Diseases, Interstitial/etiology
• Lung Diseases, Interstitial/therapy
• Smoking/adverse effects
• Bronchiolitis/etiology
• Bronchiolitis/pathology
• Lung/pathology

• Langerhans histiocytosis
• adult
• multisystem

• Cysts/complications
• Cysts/diagnostic imaging
• Female
• Humans
• Lung Diseases/diagnostic imaging
• Lung Diseases/etiology
• Middle Aged
• Tomography, X-Ray Computed

Interstitial lung diseases (ILD) are a heterogeneous group of disorders, of which many have the potential to lead to progressive pulmonary fibrosis. A distinction is usually made between primarily inflammatory ILD and primarily fibrotic ILD. As recent studies show that anti-fibrotic drugs can be beneficial in patients with primarily inflammatory ILD that is characterized by progressive pulmonary fibrosis, treatment decisions have become more complicated. In this perspective, we propose that the ‘treatable trait’ concept, which is based on the recognition of relevant exposures, various treatable phenotypes (disease manifestations) or endotypes (shared molecular mechanisms) within a group of diseases, can be applied to progressive pulmonary fibrosis. These targets for medical intervention can be identified through validated biomarkers and are not necessarily related to specific diagnostic labels. Proposed treatable traits are: cigarette smoking, occupational, allergen or drug exposures, excessive (profibrotic) auto- or alloimmunity, progressive pulmonary fibrosis, pulmonary hypertension, obstructive sleep apnea, tuberculosis, exercise intolerance, exertional hypoxia, and anxiety and depression. There are also several potential traits that have not been associated with relevant outcomes or for which no effective treatment is available at present: air pollution, mechanical stress, viral infections, bacterial burden in the lungs, surfactant-related pulmonary fibrosis, telomere-related pulmonary fibrosis, the rs35705950 MUC5B promoter polymorphism, acute exacerbations, gastro-esophageal reflux, dyspnea, and nocturnal hypoxia. The ‘treatable traits’ concept can be applied in new clinical trials for patients with progressive pulmonary fibrosis and could be used for developing new treatment strategies.

Langerhans cell histiocytosis (LCH) is a myeloid dendritic cell disorder frequently affecting children more than adults. The presentation of LCH varies with age, however, the clinical characteristics and genetic profiles of adolescent LCH remain elusive. To address the knowledge gap, we performed a single-centre retrospective study of 36 adolescent LCH patients aged between 14 and 17 years at Peking Union Medical College Hospital.

At the time of diagnosis, 10 patients were classified as unifocal single system LCH (27.8%), 2 patients had pulmonary single system LCH (5.6%), 5 patients had multifocal single system LCH with bone involvement (13.9%), and 19 patients had multisystem LCH (52.8%). The most prevalent involvement in multisystem patients was the pituitary gland (78.9%), followed by the bone (42.1%), lung (42.1%), and lymph nodes (42.1%). Eight (42.1%) patients had risk organ involvement. BRAF^N486_P490 was detected in 50% of patients who underwent next generation sequencing, and BRAF^V600E was detected in one patient. Chemotherapies were the first line treatment in 24 patients. One patient died and thirteen patients relapsed during the follow-up. The estimated 5-year OS rate and EFS rate were 94.7% and 59.0%, respectively.

In this study, we report a large series of adolescent LCH patients. The clinical characteristics of adolescent LCH patients may be close to adult LCH. Compared with pediatric cases, adolescent LCH tends to have more pituitary lesions and pulmonary involvement, fewer skin and hematopoietic involvement, a higher frequency of BRAF deletion mutation, and a lower frequency of BRAF^V600E mutation.

The online version contains supplementary material available at 10.1186/s13023-022-02436-0.

• Adolescence
• Clinical characteristic
• Genetic profiling
• Langerhans cell histiocytosis

• Adult
• Child
• Cladribine/therapeutic use
• Consensus
• Histiocytosis, Langerhans-Cell/diagnosis
• Histiocytosis, Langerhans-Cell/genetics
• Histiocytosis, Langerhans-Cell/therapy
• Humans
• MAP Kinase Signaling System
• Mutation

• 21025 Cancer Research UK
• R37 CA259260 NCI NIH HHS

• clinical manifestation
• imaging features
• prognosis
• pulmonary Langerhans cell histiocytosis
• treatment

• Adult
• Cysts
• Female
• Histiocytosis, Langerhans-Cell/diagnosis
• Histiocytosis, Langerhans-Cell/pathology
• Histiocytosis, Langerhans-Cell/therapy
• Humans
• Lung/pathology
• Male
• Retrospective Studies
• Smoking/adverse effects
• Smoking Cessation

• 2016YFC0901502 the National Key Research and Development Program of China

• BRAF
• Langerhans cell histiocytosis
• chemotherapy
• disease reactivation

• Adults
• Langerhans cell histiocytosis
• Multimodal treatment
• Prognostic factors

Pulmonary hypertension (PH) is recognized to be associated with a number of comorbid conditions. Based on these associations, PH is classified into 5 groups, considering common pathophysiologic drivers of disease, histopathologic features, clinical manifestations and course, and response to PH therapy. However, in some of these associated conditions, these characteristics are less well-understood. These include, among others, conditions commonly encountered in clinical practice such as sarcoidosis, sickle cell disease, myeloproliferative disorders, and chronic kidney disease/end stage renal disease. PH in these contexts presents a significant challenge to clinicians with respect to disease management. The most recent updated clinical classification schemata from the 6th World Symposium on PH classifies such entities in Group 5, highlighting the often unclear and/or multifactorial nature of PH. An in-depth review of the state of the science of Group 5 PH with respect to epidemiology, pathogenesis, and management is provided. Where applicable, future directions with respect to research needed to enhance understanding of the clinical course of these entities is also discussed.

• CKD - chronic kidney disease
• Group 5
• hematologic
• metabolic
• multifactorial
• pulmonary hypertension
• sarcoidosis
• sickle cell

Pulmonary Langerhans cell (LC) histiocytosis (PLCH) has unknown cause and is a rare neoplastic disorder characterized by the infiltration of lungs and various organs by bone marrow-derived Langerhans cells with an accompanying strong inflammatory response. These cells carry somatic mutations of BRAF gene and/or NRAS, KRAS, and MAP2K1 genes, which cause activation of the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) signaling pathway. PLCH occurs predominantly in young smokers, without gender predominance. Lungs might be involved as an isolated organ or as part of a multiorgan disease. High-resolution computed chest tomography plays an outstanding role in PLCH diagnosis. The typical radiological picture of PLCH is the presence of small intralobular nodules, “tree in bud” opacities, cavitated nodules, and thin- and thick-walled cysts, frequently confluent. Histological examination of the lesion and demonstration of characteristic eosinophilic granulomas with the presence of LCs that display antigen CD1a or CD207 in immunohistochemistry are required for definite diagnosis. Smoking cessation is the most important recommendation for PLCH patients, but treatment of progressive PLCH and multisystem disease is based on chemotherapy. Recently, new targeted therapies have been implemented.

• BRAF
• MAPK
• adults
• lung
• pulmonary Langerhans cell histiocytosis

Pulmonary Langerhans cell histiocytosis (PLCH) is a rare, smoking related, progressive diffuse cystic lung disease that occurs primarily in smokers. The aim of this study was to determine if there was an increase in alpha-1 antitrypsin deficient alleles or phenotypes in a large series of PLCH patients and whether serum alpha-1 antitrypsin levels correlated with markers of disease severity. Fifty PLCH patients, 24 with a diffuse cystic lung pattern and 26 with a typical nodulo-cystic pattern on imaging were included. The mean alpha-1 antitrypsin levels were in normal range for both the population with diffuse cystic lung pattern population (1.39 g/L ± 0.37) and the nodulo-cystic pattern group (1.41 g/L ± 0.21). Deficiency alleles PiZ and PiS were 1% and 2% respectively in the entire study population of 50 patients, demonstrating no increased incidence of alpha-1 antitrypsin deficiency in PLCH. Alpha-1 antitrypsin levels showed no correlation with lung function parameters or extent of cystic lesions on lung computed tomography.

Pulmonary Langerhans cell histiocytosis (PLCH) is a rare cystic lung disease. The natural history is often unpredictable making it difficult to diagnose. We report a 63-year-old male with dyspnoea, chronic cough and recurrent respiratory tract infections, who developed progressive multifocal cystic lesions on pulmonary nodule surveillance over 4 years. He was a heavy smoker with a history of multiple spontaneous pneumothoraces in his teens. Extensive investigations culminated in a thoracoscopic wedge resection, which identified histiocytic nodules staining positive for CD1a and thus confirming the diagnosis of PLCH. It is now apparent that PLCH was the likely cause of his pneumothoraces.

•

PLCH is difficult to diagnose due to its heterogeneous presentation and insidious natural history.

• CD1a
• Cystic lung disease
• Langerhans histiocytosis
• Lung nodule
• Pneumothorax

• CT scan
• Langerhans cell histiocytosis
• children
• lung

• cytarabine
• desmopressin
• diabetes
• histiocytosis
• polyuria

• Adult
• Langerhans cell histiocytosis
• Pulmonary function
• Pulmonary involvement

• Childhood
• Intensive care
• Langerhans cell histiocytosis
• Pulmonary
• Severe
• Targeted therapy

• Child
• Cohort Studies
• Histiocytosis, Langerhans-Cell/drug therapy
• Humans
• Infant
• Lung
• Retrospective Studies
• Vinblastine

• Agence Française de Sécurité Sanitaire de l'Environnement et du Travail
• Recherche et Maladie Hématologiques de l'Enfant
• Les 111 des Arts
• Association la Petite Maison dans la Prairie
• Association Histiocytose France

Diffuse cystic lung diseases include a group of heterogeneous disorders characterised by the presence of cysts within the lung parenchyma, sometimes showing a characteristic computed tomography scan pattern that allows diagnosis. The pathogenetic mechanisms underlying cyst formation in the lung are still not clear and a number of hypotheses have been postulated according to the different aetiologies: ball-valve effect, ischaemic dilatation of small airways and alveoli related to infiltration and obstruction of small vessels and capillaries that supply the terminal bronchioles and connective tissue degradation by matrix metalloproteases. A wide number of lung cyst diseases have been classified into six diagnostic groups according to the aetiology: neoplastic, congenital/genetic, lymphoproliferative, infective, associated with interstitial lung diseases, and other causes. This article focuses on lymphangioleiomyomatosis, pulmonary Langerhans cell histiocytosis and Erdheim–Chester disease, Birt–Hogg–Dubé, follicular bronchiolitis and lymphocytic interstitial pneumonia, light-chain deposition disease and amyloidosis, congenital lung disease associated with aberrant lung development and growth, and cystic lung disease associated with neoplastic lesion. These cystic diseases are epidemiologically considered as ultra-rare conditions as they affect fewer than one individual per 50 000 or fewer than 20 individuals per million. Despite the rarity of this group of disorders, the increasing use of high-resolution computed tomography has improved the diagnostic yield, even in asymptomatic patients allowing prompt and correct therapy and management without the need for a biopsy.

Diffuse cystic lung diseases show a characteristic CT scan pattern that often allows for diagnosis, even in asymptomatic patients, allowing prompt correct therapy and management without the needing of a biopsyhttps://bit.ly/2wIUKet

• Langerhans cell histiocytosis
• exercise
• lung function testing
• pulmonary hypertension

• Corticosteroid therapy
• Langerhans cell histiocytosis
• non‐smoker
• transbronchial lung cryobiopsy

The cystic lung diseases are rare orphan lung disorders that most physicians will see infrequently in their everyday practice. Diagnostic and treatment options have improved over recent decades, with opportunities for slowing rate of progression and improving outcome for patients. This review provides a summary of the clinical approach to these lung disorders, including how to differentiate between different imaging patterns, clinical features, differential diagnosis and characteristics of the commonest presenting disorders.

Cystic lung diseases are uncommon disorders with a wide differential diagnosis. Treatment has improved over the last decade and respiratory physicians should feel encouraged to investigate such cases thoroughly to reach a final diagnosis.https://bit.ly/2W6Is9D

• Langerhans cell histiocytosis
• Management
• Outcome
• Pneumothorax
• Recurrence

• Langerhans cell histiocytosis
• bronchiolitis obliterans
• mortality
• pulmonary Langerhans cell histiocytosis
• pulmonary hypertension

Langerhans cell histiocytosis (LCH) is a rare disease of unknown aetiology. While it may affect any organ of the body, few cases of solitary lung involvement are published in the literature. Here, we report a rare case of pulmonary LCH (PLCH) in an adult.

A 52-year-old male presented to hospital in July 2018 with complaints of progressively worsening cough with sputum, breathlessness, easy fatigability, and loss of appetite since 2016, and a 32-year history of heavy cigarette smoking (average 30 cigarettes/d). Physical examination showed only weakened breathing sounds and wheezing during lung auscultation. Chest computed tomography (CT) showed irregular micronodules and multiple thin-walled small holes. Respiratory function tests showed a slight decrease. Ultrasonic cardiogram showed mild tricuspid regurgitation and no pulmonary hypertension. Fibreoptic bronchoscopy was performed with transbronchial biopsies from the basal segment of right lower lobe. LCH was confirmed by immunohistochemistry. The final diagnosis was PLCH without extra-pulmonary involvement. We suggested smoking cessation treatment. A 3-mo follow-up chest CT scan showed clear absorption of the nodule and thin-walled small holes. The symptoms of cough and phlegm had improved markedly and appetite had improved. There was no obvious dyspnoea.

Imaging manifestations of nodules, cavitating nodules, and thick-walled or thin-walled cysts prompted suspicion of PLCH and lung biopsy for diagnosis.

• Pulmonary Langerhans’ cell histiocytosis
• Adult
• Smoking cessation
• Imaging
• Nodules
• Case report

• Bronchitis
• Emphysema
• Fibrosis
• Interstitial lung diseases
• Smoking

• Langerhans cell
• adult
• histiocytosis
• mitogen-activated protein kinase
• proto-oncogene protein BRAF

• Adult
• Combined Modality Therapy
• Extracellular Signal-Regulated MAP Kinases/metabolism
• Histiocytosis, Langerhans-Cell/genetics
• Histiocytosis, Langerhans-Cell/metabolism
• Histiocytosis, Langerhans-Cell/therapy
• Humans
• Mutation
• Phosphorylation
• Proto-Oncogene Mas
• Proto-Oncogene Proteins B-raf/genetics
• Randomized Controlled Trials as Topic
• Rare Diseases
• Signal Transduction

• 5-ALA
• Birbeck granules
• Histiocytosis
• Insula
• Langerhans cell

Pneumothorax often develops in pulmonary Langerhans cell histiocytosis (PLCH), but some patients take a long time to be correctly diagnosed.

This study assessed the frequency of pneumothorax in PLCH and analysed the role of chest computed tomography (CT) in the prompt diagnosis.

Of the 90 patients with PLCH seen from 2000 to 2015, 29 (32%) had pneumothorax as the initial finding. In this group, 18 (62%) patients were diagnosed within 1 month, whereas the diagnosis was delayed for 4–120 months in 11 (38%) patients.

Patients who had pneumothorax as the initial sign of PLCH tended to be younger (mean age 27.7 ± 7.92 vs. 39.9 ± 13.21 years; P = 0.0001), male (69% vs. 43%; P = 0.028), smoked less (mean pack/years 8.4 ± 6.85 vs. 19 ± 17.16; P = 0.003), and had a significantly lower mean FVC (77.96 ± 19.62 vs. 89.47 ± 21.86% pred.; P = 0.015) and FEV₁ (68.6 ± 19.93 vs. 79.4 ± 21.48% pred.; P = 0.03 than patients who had no pneumothorax. Recurrent pneumothorax was diagnosed more frequently in the group with a delayed diagnosis (82% vs. 39%; P = 0.02). CT was performed in all of the patients who were diagnosed promptly, but in none of the patients with a delayed diagnosis.

Patients who had pneumothorax as the initial sign of PLCH were younger, more frequently men, and had greater respiratory impairment than those who had no pneumothorax. CT in patients with pneumothorax led to a correct diagnosis of this disease.

• Computed tomography
• Histiocytosis
• PLCH
• Pulmonary function test

• BRAF mutation
• ITIH4
• Interleukin-1 loop model
• Interleukin-17
• Langerhans cell histiocytosis
• Langerhans cell neoplasm
• Langerhans cell sarcoma
• Merkel cell polyomavirus
• RAS/MAPK signaling pathway
• Triple-factor model

• Histiocytosis, Langerhans-Cell/pathology
• Histiocytosis, Langerhans-Cell/virology
• Humans
• Langerhans Cells/pathology
• Langerhans Cells/virology
• Merkel cell polyomavirus/physiology
• Models, Biological
• Sarcoma/pathology
• Sarcoma/virology

• HAA grant 2009 Histiocytosis Association of America
• (C) 23590426 JSPS KAKENHI (Grants-in-aid for Scientific Research)
• (C) 26460451 JSPS KAKENHI (Grants-in-aid for Scientific Research)
• (C) 17K08743 JSPS KAKENHI (Grants-in-aid for Scientific Research)
• 2010, 2011, and 2012 research grants Japan LCH Study Group