Increased serum levels of sCD40L were associated with rapidly progressive interstitial lung disease in idiopathic inflammatory myopathies.

OBJECTIVES: Whether coagulopathy exists in development of idiopathic inflammatory myopathies associated rapidly progressive interstitial lung disease (IIMs-RPILD) is unclear. In this study, we aimed to investigate soluble CD40 ligand and D-dimer levels in RPILD patients. METHODS: Patients with IIMs-ILD were enrolled and classified as RPILD and stable-ILD group. Clinical data, laboratory examinations including coagulation-associated parameters and the myositis antibodies status, chest high-resolution computed tomography (HRCT) findings and treatment regimens were collected and serum levels of sCD40L were detected by ELISA. Univariable and adjusted multivariable cox regression were performed to identify risk factors for 6-month mortality, and further to select predictors for establishing predictive model for RPILD. RESULTS: Eighty patients with IIMs-ILD were enrolled and 34 of them were diagnosed as RPILD while 46 as stable-ILD. Multivariable cox regression showed that albumin<32.4 g/L and sCD40L<1658.55 pg/ml were independent risk factors of short-term mortality in RPILD. A SMAD model consisting of serum sCD40L>1054 pg/ml, anti-MDA5 positivity, albumin<32.4 g/L and D-dimer>0.865 mg/L were generated. The odds for RPILD with SMAD score of 0, 1, 2, 3 and 4 were 0, 26.9%, 66.7%, 91.7% and 100%. The 6-month survival stratified by mild (SMAD score 0), moderate (SMAD score 1 and 2) and severe group (SMAD score 3 and 4) were 100%, 79.5% and 20%, respectively. CONCLUSIONS: We established a predictive model for IIMs-RPILD, which provided a clue that coagulopathy might exist in IIMs-RPILD and could help to better treat patients with RPILD. This model awaits further validations.

Anti-Ro52 antibodies are associated with the prognosis of adult idiopathic inflammatory myopathy-associated interstitial lung disease.

OBJECTIVES: In the present study, we aimed to assess the prevalence and clinical significance of anti-Ro52 antibodies in a cohort of patients with idiopathic inflammatory myopathy-associated interstitial lung disease (IIM-ILD) with different myositis-specific autoantibodies (MSAs). METHODS: A cohort of 267 IIM-ILD patients, including 62 patients with PM, 126 patients with DM and 79 patients with clinically amyopathic DM (CADM) were retrospectively analysed in this study. Clinical and laboratory findings, pulmonary function tests (PFTs), HRCT patterns and treatment information were compared between patients with and without anti-Ro52 antibodies. The association between prognosis and anti-Ro52 antibodies was also evaluated based on different MSA subgroups. RESULTS: Anti-Ro52 antibodies were more frequent in patients with anti-MDA5 (62.1%, P < 0.01) and anti-Jo1 (64.9%, P < 0.01) antibodies than in those with other MSAs. The proportion of patients with anti-Jo1 antibodies was higher in the anti-Ro52 antibody-positive group than in the anti-Ro52 antibody-negative group. Patients with anti-Ro52 antibodies were more likely to exhibit the Gottron sign than the anti-Ro52 antibody-negative group (P < 0.001). Furthermore, it was a predictive factor for rapid progression interstitial lung disease (RP-ILD) (P = 0.001) and was also associated with a higher mortality rate (log-rank test, P = 0.001). Furthermore, RP-ILD was more frequently exhibited in anti-MDA5- and anti-Ro52-positive patients. Moreover, anti-Ro52 antibody positivity was closely associated with a higher mortality rate in anti-MDA5-ILD patients (log-rank test, P < 0.05). CONCLUSIONS: Anti-Ro52 antibodies were highly prevalent in patients with anti-MDA5 and anti-Jo1 antibodies. Within all patients with IIM-ILD, those with anti-Ro52 autoantibodies had a higher frequency of RP-ILD and a poorer prognosis, especially in the anti-MDA5 antibody subgroup.

Cytokeratin 19 fragment is associated with severity and poor prognosis of interstitial lung disease in anti-MDA5 antibody-positive dermatomyositis.

OBJECTIVES: In the present study, we aimed to assess the clinical significance of cytokeratin 19 fragment (CYFRA21-1) in patients with anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive DM-interstitial lung disease (MDA5-DM-ILD). METHODS: A total of 73 MDA5-DM-ILD patients were retrospectively analysed in this work. Their clinical characteristics, including clinical manifestations, laboratory findings, peripheral blood lymphocyte subsets and lung function, were compared between patients with acute/subacute interstitial pneumonia (A/SIP) and chronic interstitial pneumonia (CIP). The level of serum CYFRA21-1 was also compared between the above-mentioned two groups of patients, and its association with the clinical features and mortality of MDA5-DM-ILD was also evaluated. RESULTS: Of the 73 MDA5-DM-ILD patients, 26 patients exhibited the A/SIP pattern. The level of serum CYFRA21-1 was higher in MDA5-DM patients with A/SIP compared with the CIP group (P = 0.009). Lower oxygenation index (OI), CD3+CD4+ T cell counts and percentage of CD3+CD4+ cells were also observed in MDA5-DM patients with A/SIP compared with the CIP group. Higher serum CYFRA21-1, lower OI, and lower zone consolidation were associated with a higher risk of A/SIP in MDA5-DM-ILD. In addition, 38 decedents with MDA5-DM-ILD exhibited a greater level of CYFRA21-1 compared with 35 survivors (P < 0.001). Furthermore, it was a prognostic factor and also associated with a higher mortality rate (log-rank test, P < 0.001). CONCLUSIONS: CYFRA21-1 could be a useful serum indicator associated with occurrence of A/SIP in MDA5-DM-ILD. Moreover, it was associated with a poor survival in MDA5-DM-ILD patients.

Synthesis and Structures of Polyphenylphenanthrenes.

1,2,3,4,5,6,7,8-Octaphenylphenanthrene (4) and decaphenylphenanthrene (5) were prepared by very short syntheses (two or three steps) from tetraphenylfuran and polybrominated benzene derivatives. The X-ray structures of compounds 4 and 5 show them to be quite crowded, with the phenanthrene cores twisted by about 40° due to the clash of the C4 and C5 phenyl groups. Compound 4 was resolved by chromatography on a chiral support, and its free energy of activation for racemization was determined to be 24.6 kcal mol-1 at 40 °C. Computational studies indicate that compound 5 has a racemization barrier approximately 6 kcal mol-1 lower than 4, and thus 5 would not be configurationally stable at room temperature.

Lung carcinoma with diffuse cystic lesions misdiagnosed as pulmonary langerhans cell histocytosis: a case report.

BACKGROUND: Cystic airspace is an uncommon imaging manifestation involved in non-small lung cancer (NSCLC). Diffuse cystic lesion is even rarer as pulmonary manifestation of NSCLC. In the present study, we reported a rare case of NSCLC associated with progressive diffusion of cystic lesions misdiagnosed as Pulmonary langerhans cell histocytosis (PLCH), finally diagnosed by transbronchial cryobiopsy (TBCB). CASE PRESENTATION: A 52-year-old woman was admitted to our hospital due to cough and dyspnea. High-resolution computed tomography (HRCT) presented diffuse cystic shadow mostly, concomitantly with nodular densities in bilateral lungs. A lung biopsy revealed poorly differentiated adenocarcinoma with vascular tumor emboli. The epidermal growth factor receptor (EGFR) mutation on exon 18 (G719X, G719) was detected by mutation test. The patient received treatment of tyrosine kinase inhibitor (afatinib). CONCLUSIONS: Diffuse cystic lesion can be a rare manifestation of lung cancer. It was important to improve the recognition of diffuse cystic lung diseases to avoid misdiagnosis.

Associations of Serological Biomarkers of sICAM-1, IL-1ß, MIF, and su-PAR with 3-Month Mortality in Acute Exacerbation of Idiopathic Pulmonary Fibrosis.

OBJECTIVE: To investigate prognostic values of serum biomarkers of soluble intercellular adhesion molecule 1 (sICAM-1), macrophage migration inhibitor factor (MIF), interleukin 1ß (IL-1ß), and soluble urokinase plasminogen activator receptor (su-PAR) in patients with acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF). METHODS: From August 2017 to November 2019, 122 consecutive IPF patients treated in our center were classified as stable IPF and AE-IPF based on the newly published international guidelines. Serum levels of four biomarkers at admission were measured by the enzyme-linked immunosorbent assay (ELISA). The primary endpoint was 3-month mortality. The log-rank test and logistic regression analysis were used to evaluate the effects of these biomarkers for survival in patients with AE-IPF. Cox proportional hazards analysis was performed to evaluate the prognostic values of serological biomarkers and clinical data. RESULTS: Eighty-one patients were diagnosed with stable IPF, and 41 AE-IPF patients were enrolled in the study. Serum levels of sICAM-1 (p < 0.001), IL-1ß (p < 0.001), MIF (p < 0.001), and su-PAR (p < 0.001) in patients with IPF were significantly increased compared to those in healthy controls. All the four biomarkers were elevated in patients with AE-IPF compared to those with stable IPF. The 3-month mortality in AE-IPF was 56.1% (23/41). Increased levels of MIF (p = 0.01) and IL-1ß (>5 pg/mL, p = 0.033) were independent risk factors for 3-month mortality in patients with AE-IPF. CONCLUSIONS: We showed the higher serum levels of IL-1ß, and MIF had prognostic values for 3-month mortality in AE-IPF. This study provided a clue to promote our understanding in the pathogenesis of the disease.

Correlation between serum bilirubin levels and the severity as well as the prognosis of idiopathic pulmonary fibrosis.

Bilirubin exerts antioxidant activity that has been associated with respiratory diseases. However, the relationship between serum bilirubin levels and idiopathic pulmonary fibrosis (IPF) is not clear. Therefore, in this study, we evaluated the relationship between serum bilirubin levels and the severity as well as the prognosis of IPF. One hundred and forty-six patients with IPF and 69 healthy individuals as the control group were enrolled as a derivation cohort. Routine blood examination and pulmonary function tests were performed and serum bilirubin levels were measured. To validate the value of serum bilirubin levels to predict the survival of patients with IPF, 40 additional IPF patients were included as a validation cohort. IPF patients were followed-up. Patients with IPF had significantly lower levels of serum total bilirubin (TBIL) and direct bilirubin (DBIL) than those in the control group (P < 0.05). Patients with acute exacerbation of IPF (AE-IPF) had significantly lower levels of serum TBIL and IBIL than those in patients with stable IPF (P < 0.05). The area under the receiver operating characteristic curve (AUROC) of serum TBIL levels for the prediction of the incidence of AE-IPF was 0.72 (95% CI: 0.56-0.87, P = 0.0057). The best cutoff value of serum TBIL level to predict the survival of patients with IPF was 8.8 µmol/l (AUC = 0.75, 95% CI: 0.64-0.87, P = 0.022). The log-rank test showed a significant difference in survival between the two groups (TBIL ≤8.8 µmol/l and TBIL >8.8 µmol/l) in derivation and validation cohort. Cox multiple regression analysis indicated that serum TBIL levels were an independent prognostic factor for IPF prognosis (HR = 0.582, P = 0.026). Serum TBIL levels might be useful for reflecting the severity and predicting the survival of patients with IPF.

Acute exacerbations of fibrosing interstitial lung disease associated with connective tissue diseases: a population-based study.

BACKGROUND: Acute exacerbation (AE) is the major cause of morbidity and mortality in patients with idiopathic pulmonary fibrosis (IPF). AEs also occur in other forms of fibrosing interstitial lung disease (fILD). The clinical features and prognosis of AE patients with connective tissue diseases (CTDs) associated-ILD has not been fully described. METHODS: We retrospectively reviewed 177 patients with either IPF or a characterized CTD-ILD admitted to Nanjing Drum Tower Hospital with an AE from January 2010 to December 2016. RESULTS: The study cohort included 107 subjects with AE-IPF and 70 cases with AE-CTD-ILD. Female gender, prior use of corticosteroid and immunosupressants, lower serum albumin, higher D-dimer level, TLC% pred, survival, and treatment with immunosupressants and caspofungin were more common in the CTD-ILD group (all p<0.05). The incidences of AE-CTD-ILD and AE-IPF were similar in our single center (p = 0.526). TLC% pred was the risk factor for AE after ILD diagnosis for 1 year in CTD patients (p = 0.018). Log-rank tests showed patients with CTD-ILD had a significantly lower mortality rate compared with IPF patients after AEs (p = 0.029). No significant difference in survival was noted among CTD subgroups (p = 0.353). The survival was negatively correlated with WBC count, LDH and CT score, (p = 0.006, p = 0.013 and p = 0.035, respectively), and positively correlated with PaO2/FiO2 ratio (p<0.001) in the CTD-ILD group. WBC count and PO2/FiO2 ratio were the independent predictors for survival in AE-CTD-ILD after adjusting for other clinical variates in Cox regression Models (p = 0.038 and p < 0.001, respectively). CONCLUSIONS: The clinical characteristics of patients with AE-CTD-ILD differed from those with AE-IPF, while AE incidences were similar between the two groups. Subjects with AE-CTD-fILD tended to have a better prognosis, and WBC count and PO2/FiO2 ratio were the independent survival predictors for these patients.

A long-term retrospective study of patients with biopsy-proven cryptogenic organizing pneumonia.

Cryptogenic organizing pneumonia (COP) is characterized by good response to corticosteroids, but frequent relapses after reduction or cessation of treatment are noted. The incidence, risk factors of relapse, and long-term outcomes of patients with COP remain undetermined. Patients with COP from September 2010 to December 2017 were enrolled. Hospital and office records were used as data sources. Clinical information, lab examinations, chest radiographs, treatment courses, and follow-up data were collected. Relapse group was defined as worsening of clinical manifestations in combination with progression of radiographic abnormalities in the absence of identified causes. Eighty-seven patients with COP were enrolled. Of them, 73 patients were treated with corticosteroids with relapse rate yielding 31.5% (23 of 73). Eleven patients were treated with macrolides and none of them relapsed. Fever was more common (65.2% vs. 32.0%, p = 0.004), C-reactive protein (CRP) was higher (31.5 ± 39.4 mg/L vs. 17.5 ± 32.2 mg/L, p = 0.038), and diffusion capacity for carbon monoxide (DLCO) % predicted was lower (45.9 ± 14.2% vs. 57.6 ± 18.5%, p = 0.050) in relapse group compared to nonrelapse group. Four patients who presented with organizing pneumonia (OP) as the first manifestation were ultimately diagnosed with OP secondary to autoimmune disease in follow-up. We showed relapse was common in COP patients treated with corticosteroids, but the prognosis was favorable. Fever, elevated CRP, and a reduced DLCO were related to relapse. As OP may not always be cryptogenic, a careful follow-up should be programmed to diagnose the underlying systemic disease.

Dodecaphenyltetracene.

Dodecaphenyltetracene (4), the largest perphenylacene yet prepared, was synthesized from known tetraphenylfuran, hexaphenylisobenzofuran, and 1,2,4,5-tetrabromo-3,6-diphenylbenzene in three steps. The X-ray structure of the deep red, highly luminescent 4 shows it to be a D2 -symmetric molecule with an end-to-end twist of 97°. The central acene is encapsulated by the peripheral phenyl substituents, and as a result, the molecule is relatively unreactive and even displays reversible electrochemical oxidation and reduction.

An Exceptionally Close, Non-Bonded Hydrogen-Hydrogen Contact with Strong Through-Space Spin-Spin Coupling.

Condensation of 1,8,13-tris(mercaptomethyl)triptycene and tris(bromomethyl)methane yields an in,in-cyclophane with two inwardly directed methine groups. Based on X-ray analysis and DFT and MP2 calculations, the hydrogen-hydrogen non-bonded contact distance is estimated to be 1.50-1.53 Å. Furthermore, the two in-hydrogen atoms show obvious spin-spin coupling with J=2.0 Hz.

Plasma Leptin Is Elevated in Acute Exacerbation of Idiopathic Pulmonary Fibrosis.

Background. The natural history of idiopathic pulmonary fibrosis (IPF) is very complex and unpredictable. Some patients will experience acute exacerbation (AE) and fatal outcomes. Methods. The study included 30 AE-IPF patients, 32 stable IPF (S-IPF) patients, and 12 healthy controls. We measured the plasma concentrations of leptin and KL-6. Simple correlation was used to assess associations between leptin and other variables. Plasma leptin levels were compared between AE-IPF and S-IPF subjects, decedents, and survivors. Kaplan-Meier curves were used to display survival and Cox proportional hazards regression was used to examine risk factors for survival. Results. In subjects with AE-IPF, plasma leptin was significantly greater than in subjects with S-IPF (p = 0.0003) or healthy controls (p < 0.0001). Plasma leptin was correlated with BMI, KL-6, LDH, CRP, and PaO2/FiO2 (p = 0.007; p = 0.005; p = 0.003; p = 0.033; and p = 0.032, resp.). Plasma leptin was significantly greater in 33 decedents than in the 23 survivors (p = 0.007). Multivariate Cox regression analysis showed leptin (>13.79 ng/mL) was an independent predictor of survival (p = 0.004). Conclusions. Leptin could be a promising plasma biomarker of AE-IPF occurrence and predictor of survival in IPF patients.

Occupational inhalational exposure and serum GM-CSF autoantibody in pulmonary alveolar proteinosis.

OBJECTIVES: Although the serum granulocyte-macrophage colony stimulating factor autoantibody (GMAb) levels have been recognised as a diagnostic marker in primary pulmonary alveolar proteinosis (PAP), their role in PAP with occupational inhalational exposure (PAPo) remains unclear. METHODS: Forty-five consecutive patients with PAP were enrolled. Each patient with PAP was assessed for baseline clinical characteristics, chest high-resolution CT (HRCT), serum GMAb and occupational exposure. Fifty healthy controls were included to define normal ranges for GMAb levels. Ninety-seven hospital controls with other respiratory diseases were included to establish prevalence of a history of occupational inhalation exposure. RESULTS: According to the serum GMAb cut-off value of 2.39 µg/mL, 84.4% of the recruited patients with PAP had positive serum GMAb with a median level of 28.7 µg/mL, defined as autoimmune PAP, and the remaining 15.6% had negative serum GMAb with a median level of 0.16 µg/mL, defined as non-autoimmune PAP. Also, 34.2% of patients with autoimmune PAP had a history of occupational inhalational exposure, which was not significantly higher than that of hospital controls (34.2% vs 19.6%, p=0.072). Four patients with PAPo showed negative GMAb. Their arterial oxygen tension, pulmonary function parameters and chest HRCT features were significantly different when compared with patients with autoimmune PAP (p<0.05). These four non-autoimmune occupational lung disease cases culminated in 3 deaths and a lung transplant. CONCLUSIONS: A number of patients with PAP who may have occupational inhalational exposure and negative serum GMAb represent a high possibility of silicoproteinosis and very poor survival.

[Effectiveness and safety of inhaled granulocyte-macrophage colony-stimulating factor therapy in idiopathic pulmonary alveolar proteinosis].

OBJECTIVE: To investigate the effectiveness and safety of inhaled granulocyte-macrophage colony-stimulating factor (GM-CSF) therapy in idiopathic pulmonary alveolar proteinosis (PAP). METHODS: Ten PAP patients were enrolled, who were hospitalized in the Affiliated Drum Tower Hospital of Nanjing University Medical School from January 2012 to January 2014.All the patients were treated with inhaled GM-CSF therapy, high-dose therapy for 12 weeks, GM-CSF 150 µg twice a day on days 1-7, none for days 8-14, 6 cycles, low-dose therapy for 12 weeks, GM-CSF 150 µg inhaled once a day on days 1-7, none for days 8-14, 6 cycles, and followed-up for one year. Physiologic, serologic and radiologic features of the patients were analyzed. RESULTS: After inhaled therapy, clinical symptoms, oxygenation indexes, pulmonary function of nine patients were improved, and high resolution CT (HRCT) showed ground-glass lesions reduced. After inhaled therapy for 6 months, the average level of arterial oxygen partial pressure (PaO2) was significantly higher than that before therapy ((75.5 ± 7.0) vs (63.6 ± 8.9) mmHg (1 mmHg=0.133 kPa)), while alveolar-arterial oxygen pressure difference (P(A-a)O2) was lower than before ((25.1 ± 7.1) vs (41.2 ± 13.5) mmHg) (both P<0.01). Similarly, vital capacity (VC)% predicted, forced vital capacity (FVC)% predicted and carbon monoxide diffusing capacity (DLCO)% predicted all improved after therapy ((77.3 ± 16.6)% vs (63.3 ± 16.6)%), (79.5 ± 17.6)% vs (64.9 ± 17.1)%), (69.4 ± 23.0)% vs (50.0 ± 19.9)%) (all P<0.01). The score of HRCT reduced after therapy for six months (P<0.05). While the levels of serum lactate dehydrogenase (LDH), carcinoembryonic antigen (CEA), CYFRA211 were unchanged. No serious adverse events occurred during observation. CONCLUSION: Inhaled GM-CSF therapy is safe and effective.

[The clinical significance of the levels of serum KL-6 mucin and interleukin-13 in pulmonary alveolar proteinosis].

OBJECTIVE: To explore the serum levels of KL-6 mucin and interleukin 13 (IL-13) in patients with pulmonary alveolar proteinosis (PAP) and to investigate their clinical significance. METHODS: The serum levels of KL-6 and IL-13 were measured in 54 patients with PAP and in 50 healthy volunteers. The relationships among clinical features, chest high resolution computed tomography image scores, serum KL-6 levels and serum IL-13 levels were analyzed. RESULTS: The serum levels of IL-13 in PAP patients were significantly higher than those in healthy controls [(23 ± 14) ng/L vs. (13 ± 9) ng/L, t = 3.71, P < 0.05]. The serum levels of IL-13 did not associate with lung function and image scores. The serum levels of KL-6 [median (inter quartile range) U/ml] were higher in PAP patients than those in healthy controls [3 498.50 (1 160.50-9 337.75) U/ml vs. 177.00 (147.50-255.00) U/ml, U = 6.00, P < 0.05]. The value of KL-6 negatively correlated with FVC % predicted, FEV1 % predicted, DLCO% predicted, and PaO2 (r = -0.591, -0.563, -0.529, and -0.618, P < 0.05) ; however positively correlated with serum lactate dehydrogenase, the degree of lung opacification opacity, ground glass opacity extent, ground glass opacity severity and reticulation extent (r = 0.645, 0.733, 0.500, 0.751 and 0.753, respectively, P < 0.05). The serum levels of KL-6 were higher in patients with PAP who required whole lung lavage (WLL) or inhalation of granulocyte-macrophage colony-stimulating factor (GM-CSF) than those who did not [5 592.00 (1 738.00-9 982.00) U/ml vs.1 329.00 (1 017.75-3 543.75) U/ml, U = 101.00, P < 0.05]. CONCLUSION: PAP patients had significantly higher levels of serum IL-13 and KL-6. The serum levels of KL-6 may reflect the severity of the disease and be taken as a marker of the necessity of treatment in PAP patients.

[Analysis for differences in clinical and radiologic findings between patients with cryptogenic organizing pneumonia and connective tissue disorder related organizing pneumonia].

OBJECTIVE: To investigate the difference in clinical features and radiologic findings between patients with cryptogenic organizing pneumonia (COP) and connective tissue disorder related organizing pneumonia (CTD-OP). METHODS: A total of 30 subjects with COP and 22 subjects with CTD-OP collected from 2005 to 2013 were retrospectively reviewed in the Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School, and the diagnosis of all patients were confirmed by lung biopsy. RESULTS: The common underlying diseases in patients with CTD-OP were Sjogren syndrome(SS), poly-/dermatomyositis(PM/DM), rheumatoid arthritis (RA). There were no significant differences in clinical manifestations between CTD-OP and COP. Compared with COP patients, the proportion of female patients was higher in CTD-OP. Higher positive rate for ANA was found in CTD-OP group (CTD-OP:63.6%; COP:10.0%; P<0.01). There were no significant differences in parameters of lung function between CTD-OP and COP. As to radiological findings, the most common patterns were multiple patchy, linear shadows and ground-glass opacity. Some patients showed solitary nodule or consolidation and pleural effusion. Reticular shadow was a rare pattern among these patients. Most lesions were under the pleura and/or around the bronchus. CONCLUSIONS: There are no significant differences in clinical and radiologic manifestations between COP and CTD-OP, except that the proportion of women and ANA positive rate were higher in CTD-OP.

Meta-analysis of the adverse effects of long-term azithromycin use in patients with chronic lung diseases.

The adverse effects of azithromycin on the treatment of patients with chronic lung diseases (CLD) were evaluated in the present study. MEDLINE and other databases were searched for relevant articles published until August 2013. Randomized controlled trials that enrolled patients with chronic lung diseases who received long-term azithromycin treatment were selected, and data on microbiological studies and azithromycin-related adverse events were abstracted from articles and analyzed. Six studies were included in the meta-analysis. The risk of bacterial resistance in patients receiving long-term azithromycin treatment was increased 2.7-fold (risk ratio [RR], 2.69 [95% confidence interval {95% CI}, 1.249, 5.211]) compared with the risk in patients receiving placebo treatment. On the other hand, the risk of bacterial colonization decreased in patients receiving azithromycin treatment (RR, 0.551 [95% CI, 0.460, 0.658]). Patients receiving long-term azithromycin therapy were at risk of increased impairment of hearing (RR, 1.168 [95% CI, 1.030, 1.325]). This analysis provides evidence supporting the idea that bacterial resistance can develop with long-term azithromycin treatment. Besides the increasingly recognized anti-inflammatory role of azithromycin used in treating chronic lung diseases, we should be aware of the potential for adverse events with its long-term use.

[Primary hyperparathyroidism with metastatic pulmonary calcification: a case report and review of literature].

OBJECTIVE: To highlight the characteristics of metastatic pulmonary calcification(MPC) of a patient with primary hyperparathyroidism. METHODS: The clinical, radiological, pathological and (99)mTc-MDP bone scanning data of the patient with primary hyperparathyroidism were studied and relevant literature was reviewed. RESULTS: This 56 year-old female patient presented with cough and shortness of breath. The chest CT scan showed multiple, bilateral infiltrates and calcification in the left lung and ventricular wall. Transbronchial lung biopsy was performed, and the pathological study showed that there was diffuse calcification in the alveoli and alveolar septa.(99)mTc-MDP bone-scanning showed pulmonary uptake mostly. The patient showed significant clinical and radiological improvement after surgical removal of the parathyroid gland. CONCLUSIONS: Patients of primary hyperparathyroidism with respiratory symptoms were easily misdiagnosed as primary pulmonary diseases.(99)mTc-MDP bone-scanning can be used to help differentiate MPC from other diseases with similar clinical and radiological findings, thus allowing prompt therapy.

Novel 3D-based deep learning for classification of acute exacerbation of idiopathic pulmonary fibrosis using high-resolution CT.

PURPOSE: Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is the primary cause of death in patients with IPF, characterised by diffuse, bilateral ground-glass opacification on high-resolution CT (HRCT). This study proposes a three-dimensional (3D)-based deep learning algorithm for classifying AE-IPF using HRCT images. MATERIALS AND METHODS: A novel 3D-based deep learning algorithm, SlowFast, was developed by applying a database of 306 HRCT scans obtained from two centres. The scans were divided into four separate subsets (training set, n=105; internal validation set, n=26; temporal test set 1, n=79; and geographical test set 2, n=96). The final training data set consisted of 1050 samples with 33 600 images for algorithm training. Algorithm performance was evaluated using accuracy, sensitivity, specificity, positive predictive value, negative predictive value, receiver operating characteristic (ROC) curve and weighted κ coefficient. RESULTS: The accuracy of the algorithm in classifying AE-IPF on the test sets 1 and 2 was 93.9% and 86.5%, respectively. Interobserver agreements between the algorithm and the majority opinion of the radiologists were good (κw=0.90 for test set 1 and κw=0.73 for test set 2, respectively). The ROC accuracy of the algorithm for classifying AE-IPF on the test sets 1 and 2 was 0.96 and 0.92, respectively. The algorithm performance was superior to visual analysis in accurately diagnosing radiological findings. Furthermore, the algorithm's categorisation was a significant predictor of IPF progression. CONCLUSIONS: The deep learning algorithm provides high auxiliary diagnostic efficiency in patients with AE-IPF and may serve as a useful clinical aid for diagnosis.

Pretreatment mortality risk prediction model in patients with polymyositis/dermatomyositis-associated interstitial lung disease.

OBJECTIVES: Risk prediction for patients with polymyositis/dermatomyositis-associated interstitial lung disease (PM/DM-ILD) is challenging due to heterogeneity in the disease course. We aimed to develop a mortality risk prediction model for PM/DM-ILD. METHODS: This prognostic study analysed patients with PM/DM-ILD admitted to Nanjing Drum Hospital from 2016 to 2021. The primary outcome was mortality within 1 year. We used a least absolute shrinkage and selection operator (LASSO) logistic regression model to identify predictive laboratory indicators. These indicators were used to create a laboratory risk score, and we developed a mortality risk prediction model by incorporating clinical factors. The evaluation of model performance encompassed discrimination, calibration, clinical utility and practical application for risk prediction and prognosis. RESULTS: Overall, 418 patients with PM/DM-ILD were enrolled and randomly divided into development (n=282) and validation (n=136) cohorts. LASSO logistic regression identified four optimal features in the development cohort, forming a laboratory risk score: C reactive protein, lactate dehydrogenase, CD3+CD4+ T cell counts and PO2/FiO2. The final prediction model integrated age, arthralgia, anti-melanoma differentiation-associated gene 5 antibody status, high-resolution CT pattern and the laboratory risk score. The prediction model exhibited robust discrimination (area under the receiver operating characteristic: 0.869, 95% CI 0.811 to 0.910), excellent calibration and valuable clinical utility. Patients were categorised into three risk groups with distinct mortality rates. The internal validation, sensitivity analyses and comparative assessments against previous models further confirmed the robustness of the prediction model. CONCLUSIONS: We developed and validated an evidence-based mortality risk prediction model with simple, readily accessible clinical variables in patients with PM/DM-ILD, which may inform clinical decision-making.