Vitamin-D insufficiency and sarcoidosis are more common and severe in African Americans (AA) than Caucasians. In sarcoidosis, substrate-dependent extrarenal 1,25-dihydroxyvitamin-D (1,25-(OH)2D) production is thought to contribute to hypercalciuria and hypercalcemia, and vitamin-D repletion is often avoided. However, the anti-inflammatory properties of vitamin-D may also be beneficial. We prospectively examined serum vitamin-D levels, calcium balance, and the effects of vitamin-D repletion in 86 AA and Caucasian patients with biopsy-proven active sarcoidosis from the USA (US) and Italy (IT) in university-affiliated outpatient clinics. Clinical features, pulmonary function, and calciotropic hormones were measured. 16 patients with vitamin-D deficiency and normal serum ionized calcium (Ca2+) were treated with oral ergocalciferol (50,000 IU/week) for 12 weeks. Baseline mineral parameters were similar in US (93% AA) and IT (95% Caucasian) patients irrespective of glucocorticoid treatment. Pulmonary dysfunction was less pronounced in IT patients. Nephrolithiasis (in 11% US, 17% IT patients) was associated with higher urinary calcium excretion. Vitamin-D deficiency was not more prevalent in patients compared to the respective general populations. As serum 25-hydroxyvitamin-D (25-OHD) rose postrepletion, serum 1,25-(OH)2D, γ-globulins, and the previously elevated angiotensin converting enzyme (ACE) levels declined. Asymptomatic reversible increases in Ca2+ or urinary calcium/creatinine (Ca/Cr) developed in three patients during repletion. In conclusion, Caucasian and AA patients show similar calcium and vitamin D profiles. The higher prevalence of hypercalciuria and nephrolithiasis in sarcoidosis is unrelated to endogenous vitamin-D levels. Vitamin-D repletion in sarcoidosis is generally safe, although calcium balance should be monitored. A hypothesis that 25-OHD repletion suppresses granulomatous immune activity is provided.

Background: Fractional exhaled nitric oxide (FeNO) measurement is a simple and non‐invasive method for monitoring eosinophilic airway inflammation. New portable analyzers for FeNO measurements are constantly being developed. The aim of our study was to evaluate the agreement of FeNO values measured by new portable analyzers. Materials and methods: FeNO was measured in 20 healthy subjects, 20 asthmatic and 20 chronic obstructive pulmonary disease patients using the analyzers Niox-VERO, Vivatmo-PRO and HypAir-FeNO. A linear relationship was estimated with Pearson’s coefficient (r), and absolute agreement by the intraclass correlation coefficient (ICC) and bias with the limits of agreement (95% of paired differences) were assessed according to the Bland–Altman method. Results: In the study population (58 ± 14 years, 20 females), mean values of FeNO with their 95% confidence interval were 24.0 (18.6–29.4) with the Niox-VERO, 19.6 (13.6–25.7) with the Vivatmo-PRO and 20.4 (15.7–25.1) with the HypAir-FeNO. FeNO measured with the Niox-VERO was higher than the Vivatmo-PRO (mean difference of paired values +4.3; limits −16.0 to 25.7 ppb) and the HypAir-FeNO (+3.6; −12.2 to 19.4 ppb); the Vivatmo-PRO and HypAir-FeNO showed large variability of paired differences (−0.7; −16.5 to 15.0 ppb). Measurements linearly correlated with an imperfect absolute agreement: Niox-VERO versus Vivatmo-PRO r = 0.90 and ICC = 0.87; Niox-VERO versus HypAir-FeNO r = 0.93 and ICC = 0.90, Vivatmo-PRO versus HypAir-FeNO r = 0.96 and ICC = 0.93. Most of the disagreement was greater in some asthmatic patients at high values of FeNO. Conclusions: The present study indicates that absolute exhaled NO measurements may differ to a clinically relevant extent using the Niox-VERO, Vivatmo-PRO and HypAir-FeNO analyzers. The devices cannot be used interchangeably.

Chronic obstructive pulmonary disease (COPD) is characterized by respiratory symptoms and non-reversible airflow limitation with recurrent episodes of acute exacerbations. The concurrent presence of bronchiectasis in patients with COPD is associated with reduced respiratory function as well as increased exacerbation risk. Adiponectin is a promising biomarker in COPD, as greater high molecular weight (HMW) oligomer levels have been observed among COPD patients. Here, we investigate adiponectin levels in two groups of COPD patients characterized by the presence or absence of bronchiectasis (BCO), comparing both groups to healthy controls. We evaluated serum adiponectin levels in COPD patients, those with BCO, and healthy subjects and characterized the pattern of circulating adiponectin oligomers. We found that forced volume capacity % (FVC%) and forced expiratory volume % (FEV1%) were lower for BCO patients than for COPD patients. COPD patients had higher levels of adiponectin and its HMW oligomers than healthy controls. Interestingly, BCO patients had higher levels of adiponectin than COPD patients. We showed that expression levels of IL-2, -4, and -8, IFN-γ, and GM-CSF were significantly higher in BCO patients than in healthy controls. Conversely, IL-10 expression levels were lower in BCO patients. Our data suggest that the increased levels of adiponectin detected in the cohort of BCO patients compared to those in COPD patients without bronchiectasis might be determined by their worse airway inflammatory state. This hypothesis suggests that adiponectin could be considered as a biomarker to recognize advanced COPD patients with bronchiectasis.

Background. Chronic cough is a disabling condition with a high proportion of diagnostic and therapeutic failures. Fractional exhaled nitric oxide (FeNO) has been considered a useful biomarker for predicting inhaled corticosteroids (ICS) response. We evaluated the relationship between FeNO and ICS response in chronic cough by performing a systematic review with meta-analysis. Methods. PubMed, Web of Science, Scopus and EMBASE databases were systematically searched. Differences were expressed as Odds Ratio (OR) with 95% confidence intervals (95%CI). Pooled sensitivity, specificity, positive (PLR) and negative likelihood ratio (NLR), and area under the hierarchical summary receiver operating characteristic curve (HSROC AUC ) were estimated. Results. Nine articles on 740 chronic-cough patients showed that the response rate to ICS was 87.4% (95%CI: 83.8–91.0) in 317 patients with a high FeNO and 46.3% (95%CI: 41.6–51.0) in 423 controls, with an attributable proportion of 47.0% and a diagnostic OR of 9.1 (95%CI: 3.7–22.4, p < .001). The pooled estimate of diagnostic indexes resulted in a sensitivity of 68.5% (95%CI: 46.7–84.4) and specificity of 81.9% (95%CI: 63.0–92.3), with a HSROC AUC of 0.82 (95%CI: 0.64–0.90). In a realistic scenario with a pre-test probability set at 30%, based on a pooled PLR of 3.79 (95%CI: 1.24–7.47) and NLR of 0.38 (95%CI: 0.22–0.66), the post-test probability was 62% with a high FeNO and 14% if the test was negative. Subgroup analyses confirmed a better performance for the recommended FeNO cut-off greater than 25 ppb. Meta-regression and sensitivity analyses showed no impact of major demographic and clinic variables on results. Conclusions. A high FeNO before starting ICS therapy may help identify chronic-cough patients responding to treatment, with a better performance ofhigher cut-off values. Further studies are needed to evaluate the real usefulness of this biomarker to guide cough therapy and optimise strategies in different healthcare settings (community, hospital, rehabilitation). Key messages Chronic cough is a disabling condition with a high proportion of diagnostic and therapeutic failures. Fractional exhaled nitric oxide (FeNO) may be a useful biomarker for identifying chronic cough patients who respond to steroid treatment. A FeNO cut-off lower than 25 ppb should be considered irrelevant for this clinical application.

Background: After the acute disease, convalescent coronavirus disease 2019 (COVID-19) patients may experience several persistent manifestations that require multidisciplinary pulmonary rehabilitation (PR). By using a machine learning (ML) approach, we aimed to evaluate the clinical characteristics predicting the effectiveness of PR, expressed by an improved performance at the 6-min walking test (6MWT). Methods: Convalescent COVID-19 patients referring to a Pulmonary Rehabilitation Unit were consecutively screened. The 6MWT performance was partitioned into three classes, corresponding to different degrees of improvement (low, medium, and high) following PR. A multiclass supervised classification learning was performed with random forest (RF), adaptive boosting (ADA-B), and gradient boosting (GB), as well as tree-based and k-nearest neighbors (KNN) as instance-based algorithms. Results: To train and validate our model, we included 189 convalescent COVID-19 patients (74.1% males, mean age 59.7 years). RF obtained the best results in terms of accuracy (83.7%), sensitivity (84.0%), and area under the ROC curve (94.5%), while ADA-B reached the highest specificity (92.7%). Conclusions: Our model enables a good performance in predicting the rehabilitation outcome in convalescent COVID-19 patients.