Background: Vitamin D deficiency has been associated with chronic disorders including chronic obstructive pulmonary disease (COPD) but the relationships with inflammation, exacerbations and disease progression remain unclear. Methods: In this monocentric cross-sectional observational study we analyzed the disease status, systemic inflammation, prior exacerbation frequency and loss in lung function in relation to serum 25-hydroxyvitamin D (25-OHD) levels in a cohort of 94 patients with COPD. Serum 25-OHD, C-reactive protein, interleukin-6 and tumor necrosis factor-alpha were quantified. Exacerbation frequencies and sunlight exposure were assessed. These parameters were analyzed in correlation to the current forced expiratory volume in 1 s (FEV1), the individual average 3-year FEV1 decline and the Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage. Results: We observed fair correlation between serum 25-OHD and the current FEV1 (r=0.38, P<0.001). Furthermore, mean serum 25-OHD was significantly altered between patients of GOLD stages I-IV (P=0.013). There was weak negative correlation of 25-OHD and the average annual change of the FEV1 (r=-0.26, P<0.05). Furthermore, we observed fair negative correlation between 25-OHD and C-reactive protein (r=-0.32, P<0.01) as well as weak negative correlation with interleukin-6 (r=-0.23, P<0.05). While the exacerbation frequency significantly differed between GOLD stages (P=0.04), there was no direct association between exacerbations and 25-OHD levels. Conclusion: Our data confirm frequent vitamin D deficiency in COPD and point out correlations between 25-OHD levels, systemic inflammation, disease severity and progression.

Wimms AJ, Kelly JL, Turnbull CD, McMillan A, Craig SE, O’Reilly JF, Nicol AH, Hedley EL, Decker MD, Willes LA, Calverley PMA, Benjafield AV, Stradling JR, Morrell MJ, on behalf of the MERGE trial investigators† (2020) Continuous positive airway pressure versus standard care for the treatment of people with mild obstructive sleep apnoea (MERGE): a multicentre, randomised controlled trial. Lancet Respir Med 8(4):349–358. https://doi.org/10. 1016/S2213-2600(19)30402-3

Purpose: Remote ischemic preconditioning (RIP) may protect remote organs from ischemia-reperfusion-injury (IRI) in surgical and non-surgical patients. There are few data available on RIP and lung function, especially not in healthy volunteers. The null-hypothesis was tested that RIP does not have an effect on pulmonary function when applied on healthy volunteers that were breathing spontaneously and did not experience any intervention. After approval of the Ethics Committee and informed consent of the study subjects, 28 healthy non-smoking volunteers were included and randomized in either the RIP group (n = 13) or the control group (n = 15). In the RIP group, lower limb ischemia was induced by inflation of a blood pressure cuff to a pressure 20 mmHg above the systolic blood pressure. After five minutes the blood pressure cuff was released for five minutes rest. The procedure was repeated three times resulting in 40 min ischemia and reperfusion. Capillary blood samples were taken, and lung function tests were performed at baseline (T1) and 60 min (T2) and 24 h (T3) after RIP. The control group was treated in the same fashion, but the RIP procedure was replaced by a sham protocol. Results: 60 min after RIP capillary pO(2) decreased significantly and returned to baseline level after 24 h in the RIP group. This did not occur in the control group. Capillary pCO(2), variables of lung function tests and pulmonary capillary blood volume remained unchanged throughout the experiment in both groups. Conclusion. Oxygenation is impaired early after RIP which is possibly induced by transient ventilation-perfusion inequality. No late effects of RIP were observed. The null hypothesis has to be rejected that RIP has no effect on respiratory variables in healthy volunteers.

Background/objective: The first line treatment for obstructive sleep apnea (OSA) is nasal continuous positive airway pressure (nCPAP), for which a variety of masks are available. While nasal masks (NM) are the first choice; oronasal masks (ONM) are also frequently used to prevent mouth dryness resulting from mouth opening. Our cross-sectional, prospective, randomized, un-blinded study addressed the efficacy of wearing an oral shield in addition to NM in preventing mouth leakage Methods: Patients with OSA and established therapy using NM and complaining about mouth dryness (n = 29) underwent three polysomnographies (PSGs) using NM, ONM or a nose mask in combination with an oral shield (NMS). Mask leakage was continuously documented and objective sleep quality was assessed. Results: There were significant differences in the apnea-hypopnea-index (AHI) between ONM (8.5/h; SD 6,7) and NM/nasal mask combined with oral shield device (NMS) (2.6/h; SD 2,3; 2.7/h; SD 2,6) (p < 0,05) as well as in leakage [ONM (39.7 l/min SD 12,4); NM (34.6 l/min SD 9,4); NMS (33.1 l/min SD 9,6)] (p = 0.011). Furthermore, analysis of sleep quality (NREM3) favored NM and NMS over ONM (p = 0.02). There were no significant differences between NM and NMS in any objective outcome. Conclusions: Our data consistently confirmed the NM as the first choice for continuous positive airway pressure (CPAP) therapy of OSA. Notably, we demonstrated a high potential of the oral shield for patients with mouth opening to achieve additional comfort and thereby possibly compliance, without affecting nCPAP therapy effectiveness. (C) 2019 Published by Elsevier B.V.

The role of eosinophils in coronavirus disease 2019 (COVID-19) is still a matter of debate1Lindsley A.W. Schwartz J.T. Rothenberg M.E. Eosinophil responses during COVID-19 infections and coronavirus vaccination.J Allergy Clin Immunol. 2020; 146: 1-7Abstract Full Text Full Text PDF PubMed Scopus (233) Google Scholar and eosinopenia is regarded as a negative predictive factor.2Xie G. Ding F. Han L. Yin D. Lu H. Zhang M. The role of peripheral blood eosinophil counts in COVID-19 patients.Allergy. 2020; https://doi.org/10.1111/all.14465Crossref Scopus (121) Google Scholar,3Zhao L. Zhang Y.P. Yang X. Liu X. Eosinopenia is associated with greater severity in patients with coronavirus disease 2019.Allergy. 2020; https://doi.org/10.1111/all.14455Crossref Scopus (37) Google Scholar A 60-year-old male patient with severe COVID-19 was mechanically ventilated for 6 days before transfer to our hospital. Comorbidities were hypertension and diabetes, but no allergic disorders or asthma. Body mass index was 26.3 kg/m2. He was a former smoker. Initially, C-reactive protein was 202 mg/L, procalcitonin 0.693 ng/mL, and white blood cell count 9.45 gpt/L, with normal percentages of eosinophils and lymphocytes. He received antibiotics and fluid management. Computed tomography on day 5 postintubationem (PI) showed bipulmonary ground glass opacities and basal consolidations, with marked progression on day 16 PI, necessitating extracorporeal membrane oxygenation starting on day 22 PI. Severe acute respiratory syndrome coronavirus 2 PCR was still positive on day 33 PI and negative from day 37 PI. He showed only a very slight increase in anti–severe acute respiratory syndrome coronavirus 2 antibodies in plasma, about one-third in comparison to other patients with a severe course of COVID-19. The arbitrary result of the assay amounted to 13 on day 16 PI with no significant increase in the following month (Elecsys immunoassay; Roche, Grenzach-Wyhlen, Germany; cutoff index 1.0). Bronchoalveolar lavage on day 32 PI yielded 30% lymphocytes (97% CD3+ T cells, 53% cytotoxic CD8+ CD3+ T cells), 25% neutrophils, and 36% eosinophils as well as 130 pg/mL IL-6 (Elecsys IL-6; Roche), 2.4 pg/mL IL-5 (ELISA MAX Human IL-5; BioLegend, San Diego, Calif), and 4.5 pg/mL TNF-α (Human TNF-alpha Quantikine ELISA Kit; R&D, Minneapolis, Minn). Therefore, prednisolone treatment was initiated on day 32 PI. Notably, there had been a constant increase in peripheral blood eosinophils (0% day 6 PI; 2.3% day 41 PI; peak 4.8% day 23 PI), which however did not exceed the upper limit of normal. Because of intrathoracic bleeding, thoracotomy was performed 8 days after initiation of prednisolone therapy (day 40 PI). Lung parenchyma showed marked eosinophilic vasculitis, organizing diffuse alveolar damage, patchy interstitial inflammation, and acute intraalveolar hemorrhage, without evidence for ongoing infection. This histopathologic pattern has not been described so far (Fig 1). Serum analysis confirmed hyperinflammation4Sims J.T. Krishnan V. Chang C.Y. Engle S.M. Casalini G. Rodgers G.H. et al.Characterization of the cytokine storm reflects hyperinflammatory endothelial dysfunction in COVID-19.J Allergy Clinical Immunol. 2021; 147: 107-111Abstract Full Text Full Text PDF PubMed Scopus (122) Google Scholar after viral clearance with markedly elevated IL-6 (71 pg/mL day 8 PI; 111 pg/mL day 46 PI; peak 344 pg/mL day 27 PI; Elecsys IL-6; Roche). On day 41 PI, HLA-DR–activated CD8+ T cells in the blood were increased (282/μL), B lymphocytes reduced (87/μL), and the plasma concentration of IL-5 was 0.5 pg/mL (Cytometric Bead Array Human Th1/Th2/Th17 Kit; BD, Franklin Lakes, NJ). The later result might be influenced by prednisolone therapy. Autoantibodies (antinuclear antibodies, extractable nuclear antigens, perinuclear anti-neutrophil cytoplasmic antibody, and cytoplasmic anti-neutrophil cytoplasmic antibody [indirect immunofluorescence test]) as well as anti-proteinase 3 and anti-myeloperoxidase ELISAs were negative on day 41 PI. After 2 weeks of prednisolone therapy (day 45 PI), a second BAL yielded 8% lymphocytes (52% CD3+ CD8+ cytotoxic T cells, 60.2% HLA-DR+ indicating an activated phenotype), 3% eosinophils, and 62% neutrophils as well as 175 pg/mL IL-6 (Elecsys IL-6; Roche), 2.3 pg/mL IL-5 (ELISA MAX Human IL-5; BioLegend), and 3.6 pg/mL TNF-α (Human TNF-alpha Quantikine ELISA Kit; R&D). On day 46 PI, flow cytometric analysis confirmed massive HLA-DR activation in peripheral CD8+ T cells and strong alterations in neutrophils and monocytes as well as dendritic-cell subsets. In summary, this case shows that the hyperinflammatory phase of COVID-19 may present as eosinophilic inflammation of the pulmonary vasculature without distinct peripheral eosinophilia. Pulmonary eosinophilia might be a potential therapeutic target (eg, corticosteroids and anti–IL-5 antibodies), and this case underlines the diagnostic value of BAL cytology. Furthermore, we assume that even a slight increase in peripheral eosinophils not exceeding upper limit of normal may be meaningful. Notably, the patient showed a weak humoral immune response in combination with an exceptionally strong activation of CD8+ T cells detectable in blood and BAL. Our observations indicate that besides the spectrum of hyperinflammation as described very recently,4Sims J.T. Krishnan V. Chang C.Y. Engle S.M. Casalini G. Rodgers G.H. et al.Characterization of the cytokine storm reflects hyperinflammatory endothelial dysfunction in COVID-19.J Allergy Clinical Immunol. 2021; 147: 107-111Abstract Full Text Full Text PDF PubMed Scopus (122) Google Scholar pulmonary eosinophilic vasculitis without preexisting allergic disorders may occur. The cause of the eosinophilia at this point remains elusive. Although it may indicate a type 2 response, we did not detect a significant elevation of type 2 cytokines. Altogether this case demonstrates the vast breadth of heterogeneous immunological mechanisms at play in severe COVID-19. Eosinophil responses during COVID-19 infections and coronavirus vaccinationJournal of Allergy and Clinical ImmunologyVol. 146Issue 1PreviewEosinophils are circulating and tissue-resident leukocytes that have potent proinflammatory effects in a number of diseases. Recently, eosinophils have been shown to have various other functions, including immunoregulation and antiviral activity. Eosinophil levels vary dramatically in a number of clinical settings, especially following eosinophil-targeted therapy, which is now available to selectively deplete these cells. There are key coronavirus disease 2019 (COVID-19)-related questions concerning eosinophils whose answers affect recommended prevention and care. Full-Text PDF

Importance: Nasogastric tube (NGT) placement can cause severe thoracic and non-thoracic complications, which can cause severe morbidity and mortality. The knowledge of predisposing factors is crucial for prevention of these complications. Design: We report on three different cases of severe complication of NGT placement, which have not yet been described. Results: In the first case, intrathoracic malposition of a NGT in a sliding gastric hiatus herniation and repeated insufflations of air for localization control resulted in compression and laceration of the lungs with massive pulmonary hemorrhage. In the second, there was a perforation of both the esophagus and the membranous part of the trachea from the gullet site by a guidewire-containing NGT. In the third case, severe pleuropulmonary complications occurred after short-term intrabronchial malposition. Conclusions: These cases are intended to encourage vigilance to reasons and the clinical course of thoracic complications of NGT placement. Predisposing factors and preventive measures are discussed.