OBJECTIVE: To detect the expression of plasma exosomal microRNA (miRNA) in systemic sclerosis (SSc), and to investigate its clinical significance. METHODS: A total of 20 patients who were initially diagnosed with SSc and did not receive medication in Department of Rheumatology and Immunology of Meizhou People' s Hospital from January 2020 to January 2022 were recruited, as well as 15 healthy individuals whose gender and age matched with those of the SSc patients. Plasma exosomes were isolated using ultracentrifugation method. The expression levels of exosomal miR-34-5p, miR-92-3p and miR-142-3p were detected by quantative real-time polymerase chain reaction (qRT-PCR). Correlations between the expression levels of exosomal miRNAs and clinical characteristic were analyzed by Spearman's rank correlation coefficient test. RESULTS: The mean age of 20 patients with SSc was (52.6±12.6) years, including 7 males and 13 females. Among the 20 SSc patients, 13 cases were diagnosed as limited cutaneous systemic sclerosis (lcSSc) and 7 cases were diagnosed as diffuse cutaneous systemic sclerosis (dcSSc) according to the extent of skin involvement. According to the findings of high resolution chest CT, 7 of 20 SSc patients were diagnosed with interstitial lung disease (ILD) and 13 SSc patients were diagnosed with non-ILD. The expression levels of exosomal miR-34-5p, miR-92-3p and miR-142-3p were significantly elevated in the SSc patients compared with those in the healthy controls group (P=0.003, P=0.000 1, and P=0.016, respectively). Compared with the SSc patients without ILD, the expression levels of miR-34-5p and miR-142-3p were significantly lower in the SSc patients with ILD (P=0.037 and P=0.015, respectively). The expression levels of exosomal miR-34-5p and miR-142-3p showed negative correlation with ILD (r=-0.48, P=0.031 and r=-0.55, P=0.011, respectively), and arthritis (r=-0.46, P=0.040 and r=-0.48, P=0.032, respectively). The expression levels of exosomal miR-142-3p showed a negative correlation with erythrocyte sedimentation rate (ESR) (r=-0.55, P=0.012). CONCLUSION Plasma exosomal miR-34-5p, miR-92-3p and miR-142-3p were dysregulated in SSc. The dyregulation of exosomal miR-34-5p and miR-142-3p showed correlation with SSc associated ILD (SSc-ILD).
Male ; Female ; Humans ; Young Adult ; Adult ; Clinical Relevance ; MicroRNAs/genetics* ; Scleroderma, Systemic/genetics* ; Lung Diseases, Interstitial

Humans ; Dermatomyositis/pathology* ; Interferon-Induced Helicase, IFIH1/genetics* ; Lung Diseases, Interstitial ; Autoantibodies ; Retrospective Studies

ATP-Binding Cassette Transporters/genetics* ; Follow-Up Studies ; Humans ; Infant ; Lung ; Lung Diseases, Interstitial/genetics*

Osimertinib-induced interstitial lung disease (ILD) is an uncommon, but fatal pulmonary toxicity in some patients. We report a case of a 64-year-old male with stage IV adeno-non-small cell lung cancer (NSCLC) harboring an exon 19 deletion in the epidermal growth factor receptor (EGFR) treated with osimertinib 80 mg/d for first-line targeted therapy. On day 60 after initiating treatment of osimertinib, the patient developed ILD. Osimertinib was discontinued immediately and oral prednisone 60 mg/d was initiated, ILD improved within 13 d. After balancing the risk and benefit, osimertinib was restarted concurrently with prednisone. The patient showed neither disease progression nor a recurrence of ILD for more than 16 months. Based on our case and literature review, retreatment with osimertinib under steroid coverage could be considered as an effective treatment option after careful risk-benefit assessment for patients with EGFR-mutant NSCLC.
.
Acrylamides/therapeutic use* ; Aniline Compounds/therapeutic use* ; Carcinoma, Non-Small-Cell Lung/genetics* ; ErbB Receptors/genetics* ; Humans ; Lung Diseases, Interstitial/genetics* ; Lung Neoplasms/genetics* ; Male ; Middle Aged ; Prednisone ; Protein Kinase Inhibitors/adverse effects*

ATP-Binding Cassette Transporters ; genetics ; DNA Mutational Analysis ; Humans ; Infant ; Lung ; pathology ; physiopathology ; Lung Diseases, Interstitial ; diagnosis ; genetics ; pathology ; Mutation ; genetics ; Pulmonary Alveoli ; pathology ; Pulmonary Surfactant-Associated Proteins ; deficiency ; genetics

OBJECTIVETo investigate the association of ATP-binding cassette transporter A3 (ABCA3) gene mutations with severe neonatal respiratory distress syndrome (NRDS) and lung disease in children.

METHODThirty-eight children hospitalized with respiratory disorders in Children's Hospital of Chongqing Medical University from January 2010 to December 2011 were screened. Two mutations (E292V, G1221S) in the ABCA3 gene were identified. Interstitial lung disease (ILD) was present in 10 cases, NRDS was found in 23 and congenital pulmonary dysplasia in 5 cases. There were 24 males and 14 females, with an age range of 1 hour to 15 years. Genomic DNA was prepared from blood samples and sequences were analyzed by polymerase chain reaction (PCR). Clinical feature, imaging characteristics and the results of gene detection were retrospectively analyzed.

RESULTFour cases with ABCA3 gene mutations were found; 2 patients (case 2 and case 4) had the heterozygous mutation of ABCA3 E292V. One was a 3-hour-old girl and another was a 52-day-old boy, 2 patients (case 1 and case 4) had the heterozygous mutation of ABCA3 G1221S. One was a 78-day-old boy and another was a girl, 15 years and one month old. The family history was negative for respiratory disease. Three patients (case 1, 2, 4 ) had NRDS and 2 (case 1, 2) of them were premature. One patient (case 3) had normal growth and development. She was diagnosed clinically as interstitial lung disease (ILD) after admission. The clinical outcomes of 4 cases were various. Case 1 had recurrent wheezing and inhaled corticosteroid was needed. Case 2 died because she failed to wean from mechanical ventilator. Case 3 was discharged with improvement but lost to follow-up. Case 4 grows normally.

CONCLUSIONGenetic variants within ABCA3 may be the genetic causes or background of a contributor to some unexplained refractory NRDS, and chronic lung disease developed in latter childhood. Identification of ABCA3 genetic variants in NRDS infants is important to offer genetic counseling, as well as early prognosis estimation and intervention in pediatric chronic lung disease.

ATP-Binding Cassette Transporters ; genetics ; Adolescent ; Child ; Child, Preschool ; DNA Mutational Analysis ; Exons ; Female ; Heterozygote ; Humans ; Infant ; Infant, Newborn ; Lung ; diagnostic imaging ; pathology ; Lung Diseases, Interstitial ; diagnosis ; genetics ; Male ; Mutation ; genetics ; Radiography ; Respiratory Distress Syndrome, Newborn ; diagnosis ; genetics

OBJECTIVETo report a case of I73T mutation in the pulmonary surfactant protein (SP)-C gene associated with pediatric interstitial lung disease, and study the clinical diagnosis and review related literature, to investigate the role of gene detection in the diagnosis of interstitial lung disease in infants and children.

METHODThe clinical, radiological, and genetic testing information of the case was analyzed and related literature was reviewed.

RESULT(1) An 8-month-old girl was hospitalized because of cough, tachypnea, continuous oxygen therapy and failure to thrive. Physical examination on admission revealed tachypnea, slight cyanosis and the three concave sign was positive, respiratory rate of 50 times/minute, scattered fine crackles could be heard over both lungs, clubbing fingers were found. No other abnormalities were noted. Laboratory test results: pathogenic examination was negative, multiple blood gas analysis suggested hypoxemia. Chest CT showed ground-glass like opacity, diffused tubercle infiltration. The I73T mutation in SP-C gene was identified by SP-related gene sequencing. (2) The review of related literature: Data of 3 infants with I73T mutation in SP-C gene showed that all the 3 cases had tachypnea and dyspnea, chest CT revealed diffuse infiltration or diffuse ground glass pattern in lungs, the major pathology of lungs was nonspecific interstitial pneumonia (NSIP).

CONCLUSIONA case of interstitial lung disease with I73T mutation in SP-C gene was preliminarily diagnosed in an infant. Gene test provides an important tool in the diagnosis of such pediatric interstitial lung disease.

Dyspnea ; Female ; Humans ; Idiopathic Interstitial Pneumonias ; Infant ; Lung Diseases, Interstitial ; diagnosis ; genetics ; Mutation ; Pulmonary Surfactant-Associated Protein C ; genetics ; Pulmonary Surfactants ; Tomography, X-Ray Computed

The effective and toxic ranges of anticancer drugs are very narrow and, in some cases, inverted. Thus determination of the most appropriate dosage and schedule of administration is crucial for optimal chemotherapy. In common arm trials conducted in Japan and by Southwest Oncology Group (SWOG) that used the same doses and schedules for the administration of carboplatin plus paclitaxel, the frequency of hematological toxicity was significantly higher in the Japanese trials than in the SWOG trial, despite demonstrating similar response rates. The frequency of epidermal growth factor receptor (EGFR) mutations in tumors was significantly higher among East Asian populations, and these populations are also reported to demonstrate a higher response rates to epidermal growth factor receptor tyrosine-kinase inhibitors (EGFR-TKIs). The prevalence of interstitial lung disease induced by treatment with EGFR-TKIs has been shown to be quite high in the Japanese population. Clinical trials of cetuximab against non-small cell lung cancer and of bevacizumab against stomach cancer have shown that these agents are only active in Caucasians. In a trial examining the use of sorafenib after transarterial chemoembolization in Korean and Japanese patients with advanced hepatocellular carcinoma, the compliance and dose intensity of the drug were quite low compared with other trials. Although not only identified pharmacogenomics differences but also differences in social environment, and regional medical care, including pharmacoeconomics strongly influence ethnic differences in treatment response, further identification and understanding of the pharmacogenomics underlying ethnic differences will be essential to timely and reliable global development of new anticancer drugs.
Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use ; Asian Continental Ancestry Group ; Carcinoma, Non-Small-Cell Lung/drug therapy/ethnology ; Chemoembolization, Therapeutic ; Clinical Trials as Topic ; Drug Design ; Ethnic Groups ; Humans ; Japan ; Lung Diseases, Interstitial/chemically induced ; Lung Neoplasms/drug therapy/ethnology ; Mutation ; Pharmacogenetics/*methods ; Receptor, Epidermal Growth Factor/genetics ; Republic of Korea

ATP-Binding Cassette Transporters ; genetics ; metabolism ; Animals ; Biological Transport ; Child ; DNA Mutational Analysis ; Humans ; Hypertension, Pulmonary ; genetics ; metabolism ; Lung Diseases, Interstitial ; genetics ; metabolism ; Molecular Sequence Data ; Mutation ; Polymerase Chain Reaction ; Protein Conformation ; Pulmonary Surfactant-Associated Proteins ; genetics ; metabolism ; Respiratory Distress Syndrome, Newborn ; genetics ; metabolism

OBJECTIVETo report a case of pulmonary surfactant protein (SP) gene mutation associated with pediatric interstitial lung disease, and study the clinical diagnosis process and review of related literature, to understand the relationship between interstitial lung disease and SP gene mutation in infants and children.

METHODThe clinical, radiological, histological, and genetic testing information of a case of SP gene mutation related pediatric interstitial lung disease were analyzed and related literature was reviewed.

RESULTA 2-year-old girl without a history of serious illness was hospitalized because of the shortness of breath, cough, excessive sputum, and the progressive dyspnea. Physical examination on admission revealed tachypnea, slight cyanosis, and the retraction signs were positive, respiratory rate of 60 times/minute, fine crackles could be heard through the lower lobe of both lungs; heart rate was 132 beats/minute. No other abnormalities were noted, no clubbing was found. Laboratory test results: pathologic examination was negative, multiple blood gas analysis suggested hypoxemia. Chest CT showed ground-glass like opacity, diffused patchy infiltration. Bronchoalveolar lavage fluid had a large number of neutrophils, and a few tissue cells. Eosinophil staining: negative. Fluconazole and methylprednisolone were given after admission, pulmonary symptoms and signs did not improve, reexamination showed no change in chest CT. Then lung biopsy was carried out through thoracoscopy. Histopathology suggested chronic interstitial pneumonia with fibrosis. The heterozygous mutation of R219W in the SFPTA1 and the S186N in SFTPC were identified by SP-related gene sequencing. The review of related literature showed that polymorphisms at the 219th amino acid in SP-A1 allele were found in adults with idiopathic pulmonary fibrosis (IPF), but there is no related literature in pediatric cases. The patient in this report had a mutation at the SP-A1 allele consistent with related literature. Data of 17 young children with mutation in SP-C gene showed that all the 17 cases had dyspnea and tachypnea, chest CT revealed diffuse opacities in lungs, the pathology of lungs was NSIP and CPI. There were 17 kinds of mutation and the common mutation was I73T. The mutation of S186N in SFTPC in our case has never been shown in previously published literature.

CONCLUSIONA case of interstitial lung disease with S186N gene mutation in SFTPC was preliminarily diagnosed in an infant. The SP-C gene mutations and polymorphisms are associated with pediatric interstitial lung disease.

Biopsy ; Child, Preschool ; DNA Mutational Analysis ; Dyspnea ; diagnosis ; pathology ; Female ; Humans ; Infant ; Lung ; diagnostic imaging ; pathology ; Lung Diseases, Interstitial ; diagnosis ; genetics ; pathology ; Male ; Mutation ; Pulmonary Surfactant-Associated Protein C ; genetics ; Tomography, X-Ray Computed