A randomized, placebo-controlled clinical trial evaluating olipudase alfa enzyme replacement therapy for chronic acid sphingomyelinase deficiency (ASMD) in adults: One-year results.

PURPOSE: This trial aimed to assess the efficacy and safety of olipudase alfa enzyme replacement therapy for non-central nervous system manifestations of acid sphingomyelinase deficiency (ASMD) in adults. METHODS: A phase 2/3, 52 week, international, double-blind, placebo-controlled trial (ASCEND; NCT02004691/EudraCT 2015-000371-26) enrolled 36 adults with ASMD randomized 1:1 to receive olipudase alfa or placebo intravenously every 2 weeks with intrapatient dose escalation to 3 mg/kg. Primary efficacy endpoints were percent change from baseline to week 52 in percent predicted diffusing capacity of the lung for carbon monoxide and spleen volume (combined with splenomegaly-related score in the United States). Other outcomes included liver volume/function/sphingomyelin content, pulmonary imaging/function, platelet levels, lipid profiles, and pharmacodynamics. RESULTS: Least square mean percent change from baseline to week 52 favored olipudase alfa over placebo for percent predicted diffusing capacity of the lung for carbon monoxide (22% vs 3.0% increases, P = .0004), spleen volume (39% decrease vs 0.5% increase, P < .0001), and liver volume (28% vs 1.5% decreases, P < .0001). Splenomegaly-related score decreased in both groups (P = .64). Other clinical outcomes improved in the olipudase alfa group compared with the placebo group. There were no treatment-related serious adverse events or adverse event-related discontinuations. Most adverse events were mild. CONCLUSION: Olipudase alfa was well tolerated and associated with significant and comprehensive improvements in disease pathology and clinically relevant endpoints compared with placebo in adults with ASMD.

Pulmonary function testing for the early detection of drug-induced lung disease: a systematic review in adults treated with drugs associated with pulmonary toxicity.

Pulmonary function tests (PFT) are sometimes monitored during treatment with known pulmonary toxic drugs to detect asymptomatic drug-induced interstitial lung disease (DILD). We conducted a systematic review to assess the accuracy of PFT, including the diffusing capacity for carbon monoxide (DLCO), for early detection of DILD in a range of drugs. Using a pre-specified, registered review protocol, OvidMEDLINE and EMBASE were searched from 1946 to February 2018. Two reviewers independently screened abstracts and reviewed full-text articles for inclusion. Included studies were assessed for risk of bias using adapted QUADAS-2 domains and primary outcome data were extracted and entered into RevMan5 to estimate sensitivity and specificity with 95% confidence intervals (CI). The search identified 4065 citations and included 42 studies. The most commonly studied drugs were bleomycin and amiodarone. Due to clinical heterogeneity between studies, a pooled analysis was not performed. Sensitivity of monitoring with DLCO varied between 0 and 100%, with the majority of studies finding a sensitivity of <80%. CI were wide for the majority of studies. Specificity was less than 90% in all studies. Risk of bias was high for the majority of studies for the quality domain of reference standard. The findings of this review do not support routine PFT for early detection of DILD. Due to methodological limitations, the relatively small number of participants and the low prevalence of DILD in the included studies, there remains significant uncertainty about the sensitivity of PFT to screen for DILD.

[Diffusion Capacity of the Lung and Maladaptive Post-Infarction Remodeling of the Heart].

OBJECTIVE: To assess the association of the lowering of diffusion capacity of the lung and maladaptive remodeling of the heart in a year after myocardial infarction (MI). MATERIALS AND METHODS: We included into this study 107 patients with ST elevation MI (STEMI). Examination of all patients on 7-12 th days included echocardiography (echoCG), spirography, body plethysmography, and determination of lung diffusion capacity. After one year of observation in 87 patients (81.3%) we performed echocardiogram in dynamics. RESULTS: After 1 year signs of maladaptive remodeling were detected in 25 patients (28.7%). The group of patients with remodeling had clinically significantly lowered parameters of lung diffusion function: diffusion capacity corrected for hemoglobin (DLCOcor) by 30% (p=0.001) and diffusing capacity for carbon monoxide/alveolar volume (DL/VA) by 21% (p=0.001). A mathematical model for prediction of maladaptive cardiac remodeling was obtained by the method of multivariate discriminant analysis. Univariate analysis showed that the reduction of DLCOcor was associated with 3.5-fold elevation of the risk of maladaptive remodeling in one year after STEMI. After adjustment for risk factors this risk rose up to 13.7-fold. CONCLUSION: Reduction of lung diffusion capacity below 80% of the predicted value on the 12-th day of STEMI was associated with 13.7-fold increase of the risk of detection of maladaptive remodeling of the heart after one year. Independent predictors of cardiac maladaptive remodeling were the number of diseased coronary arteries, reduced DLCO and the presence of myocardial remodeling during acute phases of myocardial infarction.

Tertiary lymphoid neogenesis is a component of pulmonary lymphoid hyperplasia in patients with common variable immunodeficiency.

BACKGROUND: Despite reducing pneumonia and other infections, antibody replacement does not appear to treat pulmonary lymphoid hyperplasia (PLH) in patients with common variable immunodeficiency (CVID). The pathogenesis and optimal treatments remain to be clarified. OBJECTIVE: We aimed to better understand the pathology of CVID-associated lung disease. Tertiary lymphoneogenesis, although a component of interstitial lung disease associated with autoimmune diseases, has not previously been explored in patients with CVID. METHODS: We examined the clinical characteristics and pathologic findings of 6 patients with CVID with nodular/infiltrative lung disease who had biopsy specimens demonstrating PLH. RESULTS: In these subjects regions of PLH contained distinct B- and T-cell zones, with B-cell predominance in 1 patient and T-cell predominance in the others. Colocalization of Ki67, Bcl6, and CD23 within this ectopic lymphoid architecture demonstrated tertiary lymphoneogenesis with active centers of cellular proliferation. One patient received rituximab with improved pulmonary radiologic findings. CONCLUSION: Ectopic lymphoid tissue forming germinal centers suggest tertiary lymphoneogenesis in CVID-associated lung disease. B cell-targeted therapy might disrupt CVID-associated lymphoid hyperplasia.

Diffusion capacity of the lung for carbon monoxide - A potential marker of impaired gas exchange or of systemic deconditioning in chronic obstructive lung disease?

Gas exchange impairment is primarily caused by ventilation-perfusion mismatch in chronic obstructive pulmonary disease (COPD), where diffusing capacity of the lungs for carbon monoxide (DLCO) remains the clinical measure. This study investigates whether DLCO: (1) can predict respiratory impairment in COPD, that is, changes in oxygen and carbon dioxide (CO2); (2) is associated with combined risk assessment score for COPD (Global Initiative for Chronic Obstructive Lung Disease (GOLD) score); and (3) is associated with blood glucose and body mass index (BMI). Fifty patients were included retrospectively. DLCO; arterial blood gas at inspired oxygen (FiO2) = 0.21; oxygen saturation (SpO2) at FiO2 = 0.21 (SpO2 (21)) and FiO2 = 0.15 (SpO2 (15)) were registered. Difference between arterial and end-tidal CO2 (ΔCO2) was calculated. COPD severity was stratified according to GOLD score. The association between DLCO, SpO2, ΔCO2, GOLD score, blood glucose, and BMI was investigated. Multiple regression showed association between DLCO and GOLD score, BMI, and glucose level (R (2) = 0.6, p < 0.0001). Linear and multiple regression showed an association between DLCO and SpO2 (21) (R (2) = 0.3, p = 0.001 and p = 0.03, respectively) without contribution from SpO2 (15) or ΔCO2. A stronger association between DLCO and GOLD score than between DLCO and SpO2 could indicate that DLCO is more descriptive of systemic deconditioning than gas exchange in COPD patients. However, further larger studies are needed. A weaker association is seen between DLCO and SpO2 (21) without contribution from SpO2 (15) and ΔCO2. This could indicate that DLCO is more descriptive of systemic deconditioning than gas exchange in COPD patients. However, further larger studies are needed.

Influence of Impaired Diffusing Capacity and Sleep-disordered Breathing on Nocturnal Hypoxemia and Health Outcomes in Men with and without Human Immunodeficiency Virus.

Rationale: Nocturnal hypoxemia is common in sleep-disordered breathing (SDB) and is associated with increased morbidity and mortality. Although impaired diffusing capacity of the lung for carbon monoxide (DlCO) is associated with daytime hypoxemia, its influence on SDB-related nocturnal hypoxemia is not known. Objectives: To characterize the effects of DlCO impairment on SDB-related nocturnal hypoxemia and associated health outcomes. Methods: Data from a multicenter cohort of men with and without human immunodeficiency virus (HIV) infection, with concomitant measures of DlCO and home-based polysomnography (n = 544), were analyzed. Multivariable quantile regression models characterized associations between DlCO and several measures of SDB-related hypoxemia (e.g., total sleep time with oxygen saturation as measured by pulse oximetry [SpO2] < 90% [T90]). Structural equation models were used to assess associations of impaired DlCO and SDB-related hypoxemia measures with prevalent hypertension and type 2 diabetes. Results: DlCO impairment (<80% predicted) was associated with sleep-related hypoxemia. Participants with severe SDB (apnea-hypopnea index ⩾ 30 events/h) and impaired DlCO had higher T90 (median difference, 15.0% [95% confidence interval (CI), 10.3% to 19.7%]) and average SDB-related desaturation (median difference, 1.0 [95% CI, 0.5 to 1.5]) and lower nadir SpO2 (median difference, -8.2% [95% CI, -11.4% to -4.9%]) and average SpO2 during sleep (median difference, -1.1% [95% CI, -2.1% to -0.01%]) than those with severe SDB and preserved DlCO. Higher T90 was associated with higher adjusted odds of prevalent hypertension (odds ratio, 1.39 [95% CI, 1.14 to 1.70]) and type 2 diabetes (odds ratio, 1.25 [95% CI, 1.07 to 1.46]). Conclusions: DlCO impairment in severe SDB was associated with sleep-related hypoxemia, prevalent hypertension, and type 2 diabetes. Assessment of SDB should be considered in those with impaired DlCO to guide testing and risk stratification strategies.

Alpha-1 Antitrypsin PI M Heterozygotes with Rare Variants: Do They Need a Clinical and Functional Follow-Up?

(1) Background: Few data are available on the risk of airway dysfunction in protease inhibitor (PI*) M heterozygotes carrying rare null or deficient allelic variants of the gene SERPINA-1 (PI*MR). (2) Methods: In this observational study, in a cohort of PI*MR heterozygotes, we evaluated respiratory functional parameters at baseline and at one-year follow-up. Moreover, we compared such parameters with those of the PI*MZ and PI*MS patients. (3) Results: A total of 60 patients were recruited; 35 PI*MR, 11 PI*MZ and 14 PI*MS. At the annual follow-up, the PI*MR and PI*MZ patients demonstrated a significantly higher FEV1 decline than the PI*MS group (p = 0.04 and p = 0.018, respectively). The PI*MR patients showed a significant increase in DLCO annual decline in comparison with the PI*MS group (p = 0.02). At baseline, the PI*MR smoking patients, compared with nonsmokers, showed statistically significant lower values of FEV1, FEV1/FVC and DLCO (p = 0.0004, p < 0.0001, p = 0.007, respectively) and, at the one-year follow-up, they displayed a significantly higher FEV1 and DLCO decline (p = 0.0022, p = 0.011, respectively). PI*MR heterozygotes with COPD showed a significantly higher FEV1, FEV1/FVC and DLCO annual decline in comparison with healthy PI*MR (p = 0.0083, p = 0.043, p = 0.041). (4) Conclusions: These results suggest that PI*MR heterozygotes, particularly smokers with COPD, have a greater annual decline in respiratory functional parameters and need to be monitored.

Association between DLCO index and the severity of heart failure: a cross-sectional study.

BACKGROUND: The prognostic role of diffusing capacity of the lung for carbon monoxide (DLCO) in heart failure has not been thoroughly investigated. Therefore, this study aimed to evaluate DLCO variation in different systolic and diastolic heart failure stages. METHODS: This was a prospective cross-sectional study on 51 patients with systolic (reduced LVEF) or diastolic (preserved LVEF) chronic heart failure (CHF). All patients underwent a standard DLCO test. The associations between the severity of heart failure and reduced carbon monoxide transfer factor (TLCO), carbon monoxide transfer coefficient (KCO), and alveolar volume (VA) were investigated. Data were analysed using SPSS software version 16. p-Values below 0.05 were considered statistically significant. RESULTS: The mean age of participants was 59.29 ± 14.91 years, with 72% of the study population being male. Systolic heart failure was observed in 47% of patients, diastolic heart failure in 18%, and a mixed systolic and diastolic pattern in 35%. There were significant differences between TLCO percentage in patients with CHF types and the New York Heart Association (NYHA) functional classes (p = 0.042). Overall, an ejection fraction (EF) of less than 25% correlated with 3%, 53%, and 0.78 declines in TLCO, KCO%, and KCO index, respectively. CONCLUSION: Despite the lack of statistically significant differences between DLCO indices and CHF severity, decreased DLCO parameters correlated with reduced EF. Therefore, DLCO testing might be helpful to predict HF severity.

Utility of serum immunoglobulin A antibody against glycopeptidolipid core antigen in the diagnosis and management of hypersensitivity pneumonitis associated with Mycobacterium avium complex: A case report.

Measurement of the levels of serum immunoglobulin A antibody against glycopeptidolipid (GPL) core antigen, a cell surface antigen found in Mycobacterium avium complex (MAC), has been reported to be useful in the diagnosis and management of pulmonary MAC infection. However, evidence on its utility in hypersensitivity pneumonitis (HP) associated with MAC (i.e., "hot-tub lung") is limited. We herein report a case of HP associated with MAC in which the GPL core antibody levels were serially measured from diagnosis to treatment and thereafter. A 61-year-old man was suspected to have non-fibrotic HP based on the clinical course, laboratory findings, imaging pattern, bronchoalveolar lavage (BAL) lymphocytosis, and histopathological findings. Based on the history of whirlpool bath use, inhalation of aerosolized MAC was suspected as the cause of HP. The GPL core antibody level, measured using an enzyme-linked immunosorbent assay kit, was elevated, suggesting an immunological sensitization to MAC. A provocation test using the patient's whirlpool bath was positive. An identical MAC strain was isolated from the BAL fluid and bathtub. Accordingly, the patient was diagnosed with HP caused by the inhalation of aerosolized MAC from the whirlpool bath. The patient recovered after steroid treatment and discontinuation of the whirlpool bath. The GPL core antibody levels decreased with disease improvement. In conclusion, GPL core antibody levels could be elevated in HP associated with MAC and decrease with disease improvement. Thus, measurement of the GPL core antibody level may be useful for the diagnosis and management of HP associated with MAC.

Postinduction therapy pulmonary function retesting is necessary before surgical resection for non-small cell lung cancer.

OBJECTIVE: Pretreatment-predicted postoperative diffusing capacity of the lung for carbon monoxide (DLCO) has been associated with operative mortality in patients who receive induction therapy for resectable non-small cell lung cancer (NSCLC). It is unknown whether a reduction in pulmonary function after induction therapy and before surgery affects the risk of morbidity or mortality. We sought to determine the relationship between induction therapy and perioperative outcomes as a function of postinduction pulmonary status in patients who underwent surgical resection for NSCLC. METHODS: We retrospectively reviewed data for 1001 patients with pathologic stage I, II, or III NSCLC who received induction therapy before lung resection. Pulmonary function was defined according to American College of Surgeons Oncology Group major criteria: DLCO ≥50% = normal; DLCO <50% = impaired. Patients were categorized into 5 subgroups according to combined pre- and postinduction DLCO status: normal-normal, normal-impaired, impaired-normal, impaired-impaired, and preinduction only (without postinduction pulmonary function test measurements). Multivariable logistic regression was used to quantify the relationship between DLCO categories and dichotomous end points. RESULTS: In multivariable analysis, normal-impaired DLCO status was associated with an increased risk of respiratory complications (odds ratio, 2.29 [95% CI, 1.12-4.49]; P = .02) and in-hospital complications (odds ratio, 2.83 [95% CI, 1.55-5.26]; P < .001). Type of neoadjuvant therapy was not associated with an increased risk of complications, compared with conventional chemotherapy. CONCLUSIONS: Reduced postinduction DLCO might predict perioperative outcomes. The use of repeat pulmonary function testing might identify patients at higher risk of morbidity or mortality.

Effects of Smoking, Obesity, and Pulmonary Function on Home Oxygen Use after Curative Lung Cancer Surgery.

Rationale: Lung cancer surgical morbidity has been decreasing, increasing attention to quality-of-life measures. A chronic sequela of lung cancer surgery is the use of postoperative oxygen at home after discharge. Prospective studies are needed to identify risk predictors for home oxygen (HO2) use after curative lung cancer surgery. Objectives: To prospectively assess risk factors for postoperative oxygen use and postsurgical morbidity in patients undergoing curative lung cancer surgery. We hypothesized that obesity, poor preoperative pulmonary function, and smoking status would contribute to the risk of postoperative oxygen use. Methods: This study included patients undergoing surgery for a first primary non-small cell lung cancer at Mount Sinai from 2016 to 2020. Univariate, multivariable logistic regression analyses and adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were assessed. Results: Of the 433 patients with diagnosed pathologic stage I non-small cell lung cancer, 63 (14.5%) were discharged with HO2. By using multivariable analyses, we found that the body mass index (BMI) (OR for a BMI of 25-30 kg/m2, 4.0; 95% CI, 1.6-11.2; OR for a BMI ⩾30 kg/m2, 6.1; 95% CI, 2.4-17.5) and the preoperative diffusing capacity of the lung for carbon monoxide (DlCO) (OR for a DlCO of <40%, 24.9; 95% CI, 3.6-234.1; OR for a DlCO of 40-59%, 3.1; 95% CI, 1.3-7.2) were significant independent risk factors associated with the risk of HO2 use after adjusting for other covariates. Although current smoking significantly increased the risk in the univariate analysis, it was no longer significant in the multivariable model. Conclusions: Obesity and the DlCO were significant as risk factors for oxygen use at home after discharge. These findings allow for identification of patients at risk of being discharged with HO2 after lung resection surgery.

Predictors of acute exacerbation in biopsy-proven idiopathic pulmonary fibrosis.

BACKGROUND: Acute exacerbation (AE) is a major cause of death in patients with idiopathic pulmonary fibrosis (IPF). Current evidence on AE-IPF has been largely based on clinical, rather than pathological, analyses. METHODS: We investigated AE incidence and its predictors using clinical, radiological, and pathological data of patients diagnosed with IPF by multi-disciplinary discussion. This study, a secondary analysis of previous research, included 155 patients with IPF who underwent surgical lung biopsy (SLB). Cumulative AE incidence was evaluated by the Kaplan-Meier method. Predictors of AE-IPF were analyzed with a Fine-Gray sub-distribution hazard model. Sub-analysis was performed using propensity score-matching analysis. RESULTS: In this cohort, the median age of the patients was 66 years and the median percent-predicted forced vital capacity was 82.8%. The cumulative AE incidence rates at 30 days and one year post SLB were 1.9% and 7.6%, respectively. On multivariable analysis, a lower percent-predicted diffusing capacity of the lung for carbon monoxide (%DLCO) (hazard ratio 0.98 per 1% increase, P = 0.02) and fibroblastic foci (FF)-present (vs. absent; hazard ratio 3.01, P = 0.04) were independently associated with a higher incidence of AE. The propensity score-matching analysis with adjustment for age, gender, and %DLCO revealed that the cumulative AE incidence rate was significantly higher in the FF-present subgroup than in the FF-absent subgroup (1-year incidence rate, 10.5% vs. 0%, respectively; P = 0.04 by Gray's test). CONCLUSIONS: FF and %DLCO were independent predictors of AE in patients with biopsy-proven IPF. FF may be associated with the pathogenesis of AE-IPF.

Thoracoscopic lobectomy for non-small-cell lung cancer in patients with impaired pulmonary function: analysis from a national database.

OBJECTIVES: The objective of this retrospective multi-institutional study was to evaluate the postoperative outcomes of video-assisted thoracoscopic surgery (VATS)-lobectomy (VATS-L) for non-small-cell lung cancer (NSCLC) in patients with impaired lung function. The second end point was to illustrate the effective role of forced expiratory volume in 1 s (FEV1%) and the diffusing capacity of the lung for carbon monoxide (DLCO%) in predicting complications in this population. METHODS: Data from patients who underwent VATS-L at participating centres were analysed and divided into 2 groups: group A comprised patients with FEV1% and/or DLCO% >60% and group B included patients with impaired lung function defined as FEV1% and/or DLCO% ≤60%. To define clinical predictors of death and complications, we performed univariate and multivariable regression analyses. RESULTS: A total of 5562 patients underwent VATS-L, 809 (14.5%) of whom had impaired lung function. The postoperative mortality rate did not differ between the 2 groups (2.3% vs 3.2%; P = 0.77). The percentage of patients who had any complication (21.4% vs 34.2%; P ≤ 0.001), the complication rate (28% vs 49.8%; P ≤ 0.001) and the length of hospital stay (P ≤ 0.001) were higher for patients with limited pulmonary function. Impaired lung function was a strong predictor of overall and pulmonary complications at multivariable analysis. CONCLUSIONS: VATS-L for NSCLC can be performed in patients with impaired lung function without increased risk of postoperative death and with an acceptable incidence of overall and respiratory complications. Our analysis suggested that FEV1% and DLCO% play a substantial role in estimating the risk of complications after VATS-L, but their role was less reliable for estimating the mortality.

Endogenous Carbon Monoxide Production and Diffusing Capacity of the Lung for Carbon Monoxide in Sepsis-Induced Acute Respiratory Distress Syndrome.

Low-dose inhaled carbon monoxide is a novel therapeutic under investigation in acute respiratory distress syndrome. The Coburn-Forster-Kane equation is a well-validated model of carbon monoxide uptake that can accurately predict carboxyhemoglobin levels to ensure safe administration of low-dose inhaled carbon monoxide in patients with acute respiratory distress syndrome. Using data from a Phase I trial of low-dose inhaled carbon monoxide, we performed a post hoc analysis to determine if the Coburn-Forster-Kane equation could be used to assess the diffusing capacity of the lung for carbon monoxide and endogenous carbon monoxide production in patients with sepsis-induced acute respiratory distress syndrome. Diffusing capacity of the lung for carbon monoxide was substantially reduced and correlated with Pao2/Fio2 and Sequential Organ Failure Assessment score. Endogenous carbon monoxide production was markedly elevated and was significantly associated with Lung Injury Score in sepsis-induced acute respiratory distress syndrome patients. Our data suggest that the Coburn-Forster-Kane equation can be used to estimate diffusing capacity of the lung for carbon monoxide and endogenous carbon monoxide production in mechanically ventilated patients. We found that increased endogenous carbon monoxide production and reduced diffusing capacity of the lung for carbon monoxide correlate with clinical endpoints associated with outcomes in patients with sepsis-induced acute respiratory distress syndrome.

Sarcoidosis in a patient clinically diagnosed with silicosis; is silica associated sarcoidosis a new phenotype?

A diagnosis of silicosis is made on the basis of exposure and typical radiological findings, according to the ILO's International Classification of Radiographs of Pneumoconiosis. Radiological patterns of silicosis can, however, resemble sarcoidosis. Sarcoidosis is a multi-systemic disorder of unknown etiology, although a role for initiating inorganic triggers such as metals or silica has been suggested. In this case report, we illustrate a patient previously diagnosed with silicosis based on exposure and radiological features, progressive under immunosuppressive treatment. In view of these findings, an open lung biopsy was performed and revealed sarcoidosis. The patient was effectively treated with infliximab. Further analysis showed the presence of silica in the granulomas. Sensitization to silica was also demonstrated, suggesting an association between silica exposure and sarcoidosis in this patient.

Clinical Manifestations, Diagnosis, and Treatment of Sarcoidosis.

The focus of this review is current knowledge about the epidemiology, clinical manifestations, diagnosis, and treatment of both pulmonary sarcoidosis and extrapulmonary sarcoidosis. Although intrathoracic involvement is the hallmark of the disease, present in over 90% of patients, sarcoidosis can affect virtually any organ. Clinical presentations of sarcoidosis are diverse, ranging from asymptomatic, incidental findings to organ failure. Diagnosis requires the presence of noncaseating granuloma and compatible presentations after exclusion of other identifiable causes. Spontaneous remission is frequent, so treatment is not always indicated unless the disease is symptomatic or causes progressive organ damage/dysfunction. Glucocorticoids are the cornerstone of treatment of sarcoidosis even though evidence from randomized controlled studies is lacking. Glucocorticoid-sparing agents and biologic agents are often used as second- and third-line therapy for patients who do not respond to glucocorticoids or experience serious adverse effects.

Unplanned postoperative reintubation following general and vascular surgical procedures: Outcomes and risk factors.

BACKGROUND: Unplanned postoperative reintubation (UPR) is a marker for severe adverse outcomes following general and vascular surgery. STUDY DESIGN: A retrospective analysis of 8809 adult patients, aged 18 years and older, who underwent major general and vascular surgery at a large single-center urban hospital was conducted from January 2013 to September 2016. Patients were grouped into those who experienced UPR and those who did not. Univariate and multivariate regression analyses were used to identify predictors of UPR, and association of UPR with adverse postoperative outcomes. All regression models had Hosmer-Lemeshow P > 0.05, and C-statistic >0.75, indicating excellent goodness-of-fit and discrimination. RESULTS: Of the 8809 patients included, 138 (1.6%) experienced UPR. There was no statistical difference in incidence of UPR between general and vascular surgery patients (p = 0.53). Independent predictors of UPR advanced age (OR 5.1, 95%CI 3.5-7.5, p < 0.01), higher ASA status (OR 7.9, 95%CI 5.6-11.1, p < 0.01), CHF (OR 7.0, 95%CI 3.6-13.9, p = 0.02), acute renal failure or dialysis (OR 3.1, 95%CI 1.8-5.7, p = 0.01), weight loss (OR 5.2, 95%CI 2.8-9.6, p = 0.01), systemic sepsis (OR 4.8, 95%CI 3.4-6.9, p < 0.01), elevated preoperative creatinine (OR 4.2, 95%CI 3.0-5.9, p = 0.01), hypoalbuminemia (OR 5.3, 95% CI 3.8-7.5, p = 0.01), and anemia (OR 4.0, 95%CI 2.8-5.9, p < 0.01). Following surgery, UPR was associated with increased mortality (OR 3.8, 95%CI 2.7-5.2, p < 0.01), pulmonary complications (OR 1.8, 95%CI 1.7-2.0, p < 0.01), renal complications (OR 2.6, 95%CI 1.7-3.5, p < 0.01), cardiac complications (OR 4.6, 95%CI 2.0-6.7, p < 0.01), postoperative RBC transfusion (OR 5.7, 95%CI 3.8-8.6,p < 0.01), and prolonged hospitalization (OR 1.8, 95%CI 1.5-2.4, p < 0.01). CONCLUSION: UPR is significantly associated with postoperative morbidity and mortality. Perioperative management aimed at decreasing incidences of UPR after noncardiac surgery should target preoperative anemia in addition to previously identified predictors.

Lung histopathological pattern in a survivor with rapidly progressive interstitial lung disease and anti-melanoma differentiation-associated gene 5 antibody-positive clinically amyopathic dermatomyositis.

Anti-melanoma differentiation-associated gene 5 (MDA5) antibodies are specific indicators of patients with dermatomyositis, particularly clinically amyopathic dermatomyositis (CADM). CADM is occasionally accompanied by fatal, treatment-resistant, rapidly-progressive interstitial lung disease (RP-ILD). All previous reports showed that histopathological findings in RP-ILD with anti-MDA5 antibody-positive CADM indicated diffuse alveolar damage (DAD). This is the first report describing a non-DAD pattern in RP-ILD with anti-MDA5 antibody-positive CADM, which was improved by immunosuppressive therapy. This case may be a milder clinical phenotype than a typical DAD pattern in RP-ILD with anti-MDA5 antibody-positive CADM.

The effect of comorbidities on COPD assessment: a pilot study.

INTRODUCTION: Patients with chronic obstructive pulmonary disease (COPD) frequently suffer from comorbidities. COPD severity may be evaluated by the Global initiative for chronic Obstructive Lung Disease (GOLD) combined risk assessment score (GOLD score). Spirometry, body plethysmography, diffusing capacity of the lung for carbon monoxide (DLCO), and high-resolution computed tomography (HR-CT) measure lung function and elucidate pulmonary pathology. This study assesses associations between GOLD score and measurements of lung function in COPD patients with and without (≤1) comorbidities. It evaluates whether the presence of comorbidities influences evaluation by GOLD score of COPD severity, and questions whether GOLD score describes morbidity rather than COPD severity. METHODS: In this prospective study, 106 patients with stable COPD were included. Patients treated for lung cancer were excluded. Demographics, oxygen saturation (SpO2), modified Medical Research Council Dyspnea Scale, COPD exacerbations, and comorbidities were recorded. Body plethysmography and DLCO were measured, and HR-CT performed and evaluated for emphysema and airways disease. COPD severity was stratified by the GOLD score. Correlation analyses: 1) GOLD score, 2) emphysema grade, and 3) airways disease and lung function parameters, described by: forced expiratory volume in the first second in percent of expected value (FEV1%), inspiratory capacity (IC%), total lung volume (TLC%), IC/TLC, and SpO2. Correlation analyses between subgroups and hierarchical cluster analysis were performed. RESULTS: Significant associations were found between GOLD score and both emphysema grade (correlation coefficients [cc]: -0.2, P=0.03) and lung function parameters (cc: -0.5 to -0.7, P-values all <0.001) weakened in patients with >1 comorbidity (cc: -0.4 to -0.5, P-values all 0.001). Significant differences between subgroups were found in GOLD score and both FEV1% (cc: -0.2, P=0.02) and IC/TLC (cc: -0.2, P=0.02). Comorbidities were associated with GOLD score and composite measures in hierarchical cluster analysis. CONCLUSION: The presence of comorbidities influences the relationship between GOLD score and lung function measurements. GOLD score may be more representative of morbidity than of COPD severity.

Vibration response imaging versus perfusion scan in lung cancer surgery evaluation.

OBJECTIVE: Ventilation/perfusion scan is a standard procedure in high-risk surgical patients to predict pulmonary function after surgery. Vibration response imaging is a technique that could be used in these patients. The objective of our study was to compare this imaging technique with the usual scanning technique for predicting postoperative forced expiratory volume. METHODS: We assessed 48 patients with lung cancer who were candidates for lung resection. Forced spirometry, vibration response imaging, and ventilation/perfusion scan were performed in patients before surgery, and spirometry was performed after intervention. RESULTS: We included 48 patients (43 men; mean age, 64 years) undergoing lung cancer surgery (32 lobectomies/16 pneumonectomies). On comparison of both techniques, for pneumonectomy, we found a concordance of 0.84 (95% confidence interval, 0.76-0.92) and Bland-Altman limits of agreement of -0.33 to +0.45, with an average difference of 0.064. By comparing postoperative spirometry with vibration response imaging, we found a concordance of 0.66 (95% confidence interval, 0.38-0.93) and Bland-Altman limits of agreement of -0.60 to +0.33, with an average difference of -0.13. CONCLUSIONS: The 2 techniques presented good concordance values. Vibration response imaging shows non-negligible confidence intervals. Vibration response imaging may be useful in preoperative algorithms in patients before lung cancer surgery.