Obesity and Insulin Resistance in Asthma Pathogenesis and Clinical Outcomes.

Common inflammatory ground links obesity, insulin resistance, and asthma. As recognition of their interplay, one worsening the natural course of the other, is recognised, questions remain about how to adequately address them altogether to improve clinical outcomes. The present manuscript sheds light on the problem, describing possible pathophysiological links, clinical views, and therapeutic challenges, raising questions about what remains to be done, and calling for multidisciplinary treatment of these patients to detect diseases early and adequately address them before they become full-blown and deteriorate their health and quality of life.

Severe and Rare Case of Human Dirofilaria repens Infection with Pleural and Subcutaneous Manifestations, Slovenia.

We report a case of human Dirofilaria repens infection in a woman in Slovenia who had concomitant pleural and subcutaneous manifestations of the infection. This case report illustrates the clinical course of a severe symptomatic parasitic infection that had multisystemic manifestations.

Gamma-glutamyltransferase is a strong predictor of secondary sclerosing cholangitis after lung transplantation for COVID-19 ARDS.

BACKGROUND: Lung transplantation (LTx) can be considered for selected patients suffering from COVID-19 acute respiratory distress syndrome (ARDS). Secondary sclerosing cholangitis in critically ill (SSC-CIP) patients has been described as a late complication in COVID-19 ARDS survivors, however, rates of SSC-CIP after LTx and factors predicting this detrimental sequela are unknown. METHODS: This retrospective analysis included all LTx performed for post-COVID ARDS at 8 European LTx centers between May 2020 and January 2022. Clinical risk factors for SSC-CIP were analyzed over time. Prediction of SSC-CIP was assessed by ROC-analysis. RESULTS: A total of 40 patients were included in the analysis. Fifteen patients (37.5%) developed SSC-CIP. GGT at the time of listing was significantly higher in patients who developed SSC-CIP (median 661 (IQR 324-871) vs 186 (109-346); p = 0.001). Moreover, higher peak values for GGT (585 vs 128.4; p < 0.001) and ALP (325 vs 160.2; p = 0.015) were found in the 'SSC' group during the waiting period. Both, GGT at the time of listing and peak GGT during the waiting time, could predict SSC-CIP with an AUC of 0.797 (95% CI: 0.647-0.947) and 0.851 (95% CI: 0.707-0.995). Survival of 'SSC' patients was severely impaired compared to 'no SSC' patients (1-year: 46.7% vs 90.2%, log-rank p = 0.004). CONCLUSIONS: SSC-CIP is a severe late complication after LTx for COVID-19 ARDS leading to significant morbidity and mortality. GGT appears to be a sensitive parameter able to predict SSC-CIP even at the time of listing.

Case report: Congenital extrahepatic portocaval shunt presenting as pulmonary arterial hypertension in a pregnant patient.

Congenital extrahepatic portocaval shunt (CEPS) is a rare condition in which a rare congenital vascular anomaly of the portal system is present. CEPS may manifest as pulmonary arterial hypertension (PAH). When diagnosed and treated early, PAH can be reversible. We report a case of a previously asymptomatic woman, who manifested with severe pulmonary hypertension during pregnancy and was consequently diagnosed with CEPS. After unsuccessful medical treatment, urgent lung transplantation was done.

Lung Transplantation for End-Stage Respiratory Failure After Severe COVID-19: A Report of 2 Cases.

We report 2 cases of bilateral lung transplantation for nonresolving coronavirus disease 2019 associated respiratory failure. In the first patient, the severe acute respiratory syndrome coronavirus 2 infection caused acute respiratory distress syndrome requiring prolonged extracorporeal membrane oxygenation support; in the second patient, coronavirus disease 2019 resulted in irreversible pulmonary fibrosis requiring only ventilatory support. The 2 cases represent the 2 ends of the spectrum showing significant differences in preoperative and postoperative courses.

Urgent lung transplantation for thymic neoplasm-associated severe constrictive bronchiolitis with bronchiectasis and radiotherapy-induced organizing pneumonia: A case report.

Here, we present the case of a 28-year-old woman who developed severe and progressive thymoma-associated constrictive bronchiolitis with bronchiectasis, despite undergoing thymectomy. The disease was further complicated by radiation-induced organizing pneumonia (RIOP), which developed after adjuvant radiotherapy (RT) for Masaoka stage II thymoma. The patient was successfully treated with an urgent lung transplantation (LTx) for irreversible respiratory failure.

Clinical and spirometric variables are better predictors of COPD exacerbations than routine blood biomarkers.

BACKGROUND: Understanding the risk factors for exacerbations of COPD may help provide a more personalised approach to exacerbation prevention. METHOD: Observational, prospective, international, multicentre study aimed at identifying risk factors for exacerbations of COPD. Clinical variables, lung function and CAT scores were collected at baseline. In addition, routine blood biomarkers were also obtained, and patients were followed for 12 months. RESULTS: A total of 326 patients were included. Of these, 155 (47.5%) presented at least one exacerbation. The median time to the first exacerbation was 147 days. Exacerbators had more respiratory symptoms, more impairment in FEV1(%), FVC(%) and a worse CAT score. Regarding biomarkers, only C-reactive protein was significantly higher in exacerbators (2.8 (standard deviation (SD):3.8) mg/dL vs. 1.9 (SD:2.6) mg/dL; p = 0.037). In multivariate analysis, only CAT scores, FEV1(%) and previous exacerbations were significantly associated with having an exacerbation during follow-up. In the equation of risk, patients with a CAT score ≥15, FEV1(%) <55% and at least one exacerbation the previous year had a probability of 76% of having an exacerbation during the next year, compared with 17% in patients who had none of the previous variables. No biomarkers showed a significant association in multivariate analysis. CONCLUSIONS: Less than half of the patients presented an exacerbation during the one-year follow-up. CAT scores, FEV1(%) and previous exacerbations were the only variables associated with increased risk of exacerbations. Routine biomarkers did not provide additional information to evaluate the risk of exacerbations.

Acute interstitial pneumonia triggered by strenuous exercise.

Acute interstitial pneumonia (AIP) is a rare and severe form of idiopathic interstitial lung disease. Treatment is primarily supportive with supplemental oxygenation and mechanical ventilation. Prognosis is poor, but long-term survival is possible after recovery from AIP. We present a case of a 48-years-old previously healthy female who was admitted due to acute shortness of breath and respiratory failure which started three days after she ran a half-marathon. After excluding infectious causes and connective-tissue diseases, a presumptive diagnosis of AIP was made based on clinical and radiological characteristics. The patient was successfully treated with high-dose corticosteroids and mycophenolate mofetil.

Association Between Routine Blood Biomarkers and Clinical Phenotypes and Exacerbations in Chronic Obstructive Pulmonary Disease.

Introduction: Chronic obstructive pulmonary disease (COPD) is associated with increased lung and systemic inflammation. We aimed to identify associations between easy-to-obtain blood biomarkers and the frequency and severity of exacerbations. Methods: Cross-sectional, multicentre study performed in four centres in Spain, Italy, Bulgaria, and Slovenia. Blood samples were obtained for blood cell count, C-reactive protein (CRP), alpha-1 antitrypsin (AAT) and fibrinogen analysis. The neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR) and eosinophil/basophil ratio (EBR) were calculated. Firstly, patients were divided into clinical phenotypes according to the Spanish guidelines of COPD, and secondly, patients were classified into 2 groups: non-exacerbators (≤1 ambulatory exacerbation in the previous year) and exacerbators (≥2 ambulatory exacerbations or 1 hospitalisation in the previous year). A multivariate stepwise logistic regression model was performed to identify laboratory parameters associated with exacerbators. Results: A total of 355 patients with a mean age 66 years (SD=8.9) were included, and 64% were male. The mean FEV1% (forced expiratory volume in the first second) was 55% (SD=20%), and the mean COPD Assessment Test (CAT) score was 15.6 (SD=7.9). One hundred ninety-six (55.2%) patients were classified in the non-exacerbator group, and 159 (44.8%) were exacerbators. Patients in the exacerbators group presented lower haemoglobin levels (p=0.019) and ERB (p= 0.023) but higher CRP levels (p=0.001). In the multivariate analysis, females, higher levels of CRP, lower FEV1% and low EBR were independently related to exacerbators. Conclusion: Female sex, having a more severe impairment of lung function, higher CRP levels and a lower EBR are associated with an exacerbator phenotype in COPD.

Chitotriosidase Activity in Plasma and COPD Exacerbations.

INTRODUCTION: This study aimed to determine the association between plasma chitotriosidase activity and the clinical characteristics and exacerbation rate of COPD patients. METHODS: The study comprised 97 patients with COPD. Their clinical characteristics and a history of exacerbations in the last 12 months were noted. Plasma chitotriosidase activity was determined. Patients were followed up for 12 months, and the number of moderate and severe exacerbations during this period was recorded. RESULTS: Chitotriosidase activity positively correlated with patient age (rho = 0.217, p = 0.036) and inversely with CAT (rho = - 0.240, p = 0.020). There was no correlation with lung function. Chitotriosidase activity was significantly lower in patients with a history of ≥ 2 exacerbations compared to patients without a history of exacerbations (93 [38-312] vs. 264 [168-408] nmol/h/mL, p = 0.033). Overall, there was no difference in chitotriosidase activity between patients with or without observed exacerbations. Patients with a history of ≥ 1 exacerbation and ≥ 1 observed exacerbation had higher chitotriosidase activity compared to patients without further exacerbations (240 [144-456] vs. 52 [39-240] nmol/h/mL, p = 0.035). Multivariate analysis identified FEV1 (HR 0.976, 95% CI 0.956-0.996, p = 0.016) and blood eosinophil percentage (HR 1.222, 95% CI 1.048-1.424, p = 0.011) as independent predictors of future exacerbations in the total patient population, while in patients with a history of ≥ 1 exacerbation ,the only independent predictor was chitotriosidase activity (HR per 10 nmol/h/mL 1.028, 95% CI 1.002-1.055, p = 0.037). CONCLUSION: While mixed associations between chitotriosidase activity and clinical outcomes were seen, chitotriosidase activity could be a predictor of future exacerbations in patients with a history of ≥ 1 exacerbation in the past  12 months.

Should Patients Switched from D to B in the GOLD 2017 Classification be Discontinued from Inhaled Corticosteroids?

Inhaled corticosteroids (ICSs) are the cornerstone of the treatment of asthma, but their role in COPD is limited. Several guidelines recommend their use in patients with severe airflow limitation, frequent exacerbations and asthma-COPD overlap (ACO), while the previous GOLD document recommended ICS for patients with high risk of exacerbations and a high level of symptoms (group D). Following the changes in the GOLD document 2017 update, in which impaired lung function is no longer considered as a determinant of exacerbation risk, a high number of COPD patients can now be labeled as group B (low risk of exacerbations and high level of symptoms) instead of D, and hence, no longer fulfill the indication for ICS. Since long-term therapy with ICS can entail secondary effects, the withdrawal of this treatment should be considered in this group of patients. In this article, we summarize the evidence for discontinuation of ICS in this subgroup of patients and provide suggestions for clinicians on the appropriate use on ICS in patients moving from D to B.

Bronchoalveolar lavage chitotriosidase activity as a biomarker of sarcoidosis.

BACKGROUND: Chitotriosidase (CTO) was shown to be a good biomarker of sarcoidosis. Increased levels in bronchoalveolar lavage fluid (BALF) were reported and associated with more severe forms of the disease. OBJECTIVES: The aim of the study was to evaluate the value of CTO in BALF as a routine biomarker of sarcoidosis. METHODS: The study included 85 patients in 9 control subjects in whom serum and BALF CTO were measured. RESULTS: Significantly higher CTO levels were detected in BALF of sarcoidosis patients than in control subjects (p < 0.001). There was good correlation between serum and BALF CTO levels in sarcoidosis patients (Spearman's Rho 0.481, p < 0.001). Serum but not BALF CTO had good correlation with clinical parameters. Only in a group of patients with BALF CTO above upper normal range there was association of BALF CTO with impaired FVC (p = 0.020) and chest radiograph score (0-2 vs. 3-4, p = 0.016). CONCLUSIONS: In comparison to serum CTO no additional benefit of determining CTO in BAL for routine sarcoidosis workup was shown.

Common chitotriosidase duplication gene polymorphism and clinical outcome status in sarcoidosis.

BACKGROUND: Chitotriosidase has been found to be useful as a sarcoidosis biomarker. In patients with better outcome lower values were observed. Some subjects have 24-base pair duplication in the chitotriosidase gene (CHIT1) that results in the production of inactive enzyme. This might influence the outcome of sarcoidosis and account for described observations. OBJECTIVES: The aim of this study was to correlate common CHIT1 duplication polymorphism and clinical outcome status in sarcoidosis (COS). METHODS: This retrospective study comprised 180 patients with sarcoidosis. COS at 3, 5 and 10 years was determined and correlated with CHIT1 24-base pair duplication polymorphism. CHIT1 genotyping was done by the PCR method. RESULTS: There was no significant correlation between CHIT1 24-base pair duplication polymorphism and COS at 3, 5 or 10 years but a subgroup analysis showed higher frequency of patients with Loefgren's syndrome (50% vs. 17.1%) and better COS in CHIT1 24-base pair duplication homozygotes vs. all other subjects in major COS groups (no, minimal and persistent disease) at 3 years (p=0.025) and borderline significant at 5 years (p = 0.090). CONCLUSIONS: In this study no correlation between CHIT1 24-base pair duplication polymorphism and COS was shown, but possible protective role of homozygous condition for CHIT1 24-base pair duplication polymorphism is suggested.

Serial chitotriosidase measurements in sarcoidosis--two to five year follow-up study.

INTRODUCTION: Chitotriosidase (CTO) is a human chitinolytic enzyme secreted by activated macrophages and polymorphonuclear neutrophils. Albeit not specific for sarcoidosis, it is increased in over 90% of patients with active disease. The aims of this study were to correlate CTO measurements with clinical assessment of sarcoidosis and to test CTO as a marker of sarcoidosis relapse. METHODS: 95 patients were followed-up for 24-60 months. Serial CTO measurements were performed every 3-6 months and correlated to clinical symptoms, lung function (FVC and DLco) and chest X-ray. In 38 patients clinical outcome status (COS) at 5 years was determined. RESULTS: Initial CTO levels were significantly higher in patients with impaired FVC/DLco (p = 0.011 for both) but there was no correlation with standard chest X-ray stages. Patients with Loefgren's syndrome had significantly lower initial and control CTO level compared to other patients (p = 0.011 and p = 0.001, respectively). At follow-up there was a positive correlation of CTO and deterioration of clinical symptoms (p < 0.001), chest X-ray (p < 0.001) and FVC/DLco (p = 0.012 and p = 0.086, respectively). Control CTO levels were significantly lower in no disease groups versus minimal or persistent disease group as defined by COS (p = 0.003 and p < 0.001, respectively). At relapse CTO increased for 100% or more from baseline value in 12/14 patients. CONCLUSIONS: It was shown that CTO correlates with certain sarcoidosis phenotypes (Loefgren's syndrome, COS) and that serial measurements of CTO correlate with clinical symptoms, chest radiographs and lung function.

Phrenic nerve conduction studies in patients with chronic obstructive pulmonary disease.

INTRODUCTION: The most common etiology of hypercapnic respiratory failure is chronic obstructive pulmonary disease (COPD). However, the differential diagnosis also includes neuromuscular disorders. We studied the specificity of reduced amplitude phrenic nerve compound motor action potential (CMAP) to diagnose neuromuscular disorders. METHODS: A group of patients with advanced COPD were recruited prospectively and compared with controls. Phrenic nerve CMAPs were measured bilaterally using supraclavicular surface stimulation and bipolar recording (G1: 5 cm above the xiphoid; G2: 16 cm from G1). RESULTS: A group of 20 patients (15 men) and a group of 29 controls (15 men) were included. Phrenic nerve CMAPs of patients with COPD had significantly longer latency and higher amplitude. CONCLUSION: Our study demonstrates that patients with hypercapnic respiratory failure and reduced phrenic nerve CMAP amplitude most probably have a neuromuscular disorder affecting the diaphragm and not COPD or another lung disorder.

Fungal exposure in homes of patients with sarcoidosis - an environmental exposure study.

BACKGROUND: There is increasing evidence that exposure to moulds (fungi) may influence the development of sarcoidosis. To assess the influence of the environmental exposure, a study was undertaken to determine the exposure to fungi in homes of subjects with sarcoidosis. METHODS: Subjects were patients with clinically established sarcoidosis recruited during the period September 2007 till June 2010. Of these 55 were newly diagnosed and currently under treatment for less than one year, 25 had been treated and had no recurrence and 27 had been treated but had recurrence of the disease. Controls were healthy subjects without any respiratory symptoms (n = 30). Samples of air (about 2.5 m3) were taken in the bedroom of the subjects using a portable pump and cellulose ester filters. The filters were analysed for the content of the enzyme N-acetylhexosaminidase (NAHA) as a marker of fungal cell biomass, using a specific substrate and a fluorescent technique and expressed as NAHA units (U)/m3. RESULTS: Compared to controls, subjects undergoing treatment of the disease (newly diagnosed or with recurrence) had significantly higher activities of NAHA in their homes than controls (33.6 and 39.9 vs 10.0 U/m3, p < 0.001 and <0.001). Among controls only 5 out of 30 subjects had levels of NAHA above the second quartile value (14 U/m3). In homes of subjects with newly diagnosed disease with treatment less than one year, values above 14 NAHA U/m3 were found among 35 out of 55 and among those with recurrent disease among 18 out of 27. CONCLUSIONS: The higher activities of NAHA enzyme found in homes of subjects with active and recurrent sarcoidosis suggest that exposure to fungi is related to the risk of sarcoidosis. Further environmental studies to assess the importance of this exposure for subjects with sarcoidosis are warranted. The results suggest that remedial actions in homes with high levels of fungi may be justified.

Ex vivo study of altered mitral apparatus geometry in functional mitral regurgitation.

BACKGROUND: Functional mitral regurgitation (FMR) in patients with ischemic or nonischemic cardiomyopathy has been related to several overlapping factors. In vivo, these factors are very difficult to study independently of dynamic processes, such as ventricular wall motion or annular contraction. We developed an ex vivo left ventricular model that allows independent variations of annular size, papillary muscle (PM) position, and transvalvular pressure. We tested the hypothesis that FMR is a consequence of an altered balance of the tethering and coapting forces acting on leaflets. METHODS: Measurements were made on 4 excised porcine valves under physiological pressures and flows. Testing was done by systematically varying annular size and PM position. We evaluated 3 annulus sizes (normal, 15% dilation, and 25% symmetric dilation) by sequentially displacing PMs in lateral, posterolateral, and apicoposterolateral positions. RESULTS: Our results show that annular dilation is a major determinant of mitral regurgitation. Displacement of PMs also affects the regurgitant flow, but to a much lesser degree. Apical and posterolateral PM displacement increases regurgitant flow to a higher degree than isolated lateral or posterolateral displacement. Increased transvalvular pressure decreases regurgitant flow for any given geometric configuration of the mitral valve (MV). CONCLUSION: Clinically observed pathologic configurations of the MV can be accurately reproduced ex vivo by altering the tethering and coapting forces acting on mitral leaflets. Our results support the mechanism of mitral regurgitation in which increased tethering forces and decreased coapting forces acting on the leaflets create the regurgitant orifice.

Fire-eater's lung complicated by an infectious abscess requiring surgical treatment.

We describe a case of fire-eater's pneumonia that was complicated by an infectious lung abscess with substantial haemoptysis. Conservative treatment was inadequate. Surgical resection was necessary and proved to be successful.

Regurgitant flow in ischemic and dilative mitral regurgitation.

BACKGROUND AND AIM OF THE STUDY: It is well established that there are geometric differences between ischemic and dilative mitral regurgitation (MR), yet data on the hemodynamic consequences of these differences are scarce. The study aim was to determine whether mitral regurgitant flows in ischemic MR differ from those in dilative MR. METHODS: A left heart simulator was developed to evaluate possible differences in regurgitant flows between two pathological mitral valve configurations, ischemic and dilative. Ischemic MR was simulated by increasing the baseline intercommissural diameter (CC) by 10%, the baseline septolateral (SL) diameter by 30%, and by displacing the posteromedial papillary muscle (PM) to the apical posterolateral position. Dilative MR was simulated by increasing the baseline SL and CC diameters by 30%, and by a symmetrical displacement of both PMs. Mitral regurgitant flow measurements were carried out under transmitral pressures ranging from 40 to 140 mmHg (increments of 15 mmHg). Camera snapshots of the mitral annulus were used to accurately determine mitral annular geometry by measuring the SL and CC diameters. RESULTS: A total of 24 measurements was made on four porcine mitral valves; 14 to evaluate ischemic MR, and 10 to evaluate dilative MR. In ischemic MR, a constant regurgitant flow was observed throughout the pressure range tested. In dilative MR, increasing the transmitral pressure caused the regurgitant flows to decrease exponentially. The mitral annulus snapshot analysis showed that displacement of the posteromedial PM in ischemic MR caused the regurgitation orifice to appear at the tented side of the valve. An additional regurgitation orifice was formed through bulging (prolapse) of the leaflets at the contralateral commissure. The phenomenon was not observed in the dilative mitral valve configuration, where a central regurgitation orifice appeared with symmetrical PM displacement. CONCLUSION: These data suggest that geometric differences between ischemic and dilative MR translate into significantly different hemodynamic properties of insufficient mitral valves.