Comparison of pulmonary function test, diffusion capacity, blood gas analysis and CT scan in patients with and without persistent respiratory symptoms following COVID-19.

BACKGROUND: Long-lasting symptoms following SARS-CoV2-infection have been described in several studies. However, there is only limited knowledge about the ongoing pathophysiology and the association with pathological findings in medical examinations. METHODS: In this post hoc analysis of a prospective trial, 135 patients following COVID-19 were enrolled and grouped with respect to the presence or absence of respiratory ongoing symptoms following COVID-19. Pulmonary function test (PFT), diffusion capacity measurement (TLCO SB and TLCO/VA), blood gas analysis (BGA), laboratory tests and high-resolution computed tomography (HRCT) of patients with persistent respiratory symptoms were compared to those of asymptomatic patients. RESULTS: In this analysis, 71% (96/135) of all patients (mean age 49 years; range 20-91 years) reported long-lasting symptoms after a median (IQR) of 85 days (60-116) following COVID-19 whereby 57.8% (78/135) complained about persistent pulmonary symptoms. Pathological findings in blood test, PFT, TLCO, BGA and/or HRCT were found in 71.8% and 64.1% of patients with and without long-lasting respiratory symptoms respectively. Patients with persistent respiratory symptoms were significantly younger and presented a significant lower FVC (%), TLC (L), and TLCO SB compared to asymptomatic patients (p < 0.05). The multiple logistic regression results in a significant effect of age (p = 0.004) and TLCO SB (p = 0.042). CONCLUSION: Following COVID-19, a large proportion of patients experience ongoing symptoms, whereby the respiratory symptoms are the predominant complaints. Compared to asymptomatic patients, patients with ongoing symptoms were younger and presented a significant lower FVC, TLC and TLCO SB. The multiple logistic regression demonstrated only a significant association between the TLCO SB as the only PFT parameter and the perceived symptoms.

Does Regular Physical Activity Mitigate the Age-Associated Decline in Pulmonary Function?

Whereas the negative effects of aging and smoking on pulmonary function are undisputed, the potential favorable effects of physical activity on the aging process of the otherwise healthy lung remain controversial. This question is of particular clinical relevance when reduced pulmonary function compromises aerobic exercise capacity (maximal oxygen consumption) and thus contributes to an increased risk of morbidity and mortality. Here, we discuss whether and when the aging-related decline in pulmonary function limits maximal oxygen consumption and whether, how, and to what extent regular physical activity can slow down this aging process and preserve pulmonary function and maximal oxygen consumption. Age-dependent effects of reduced pulmonary function (i.e., FEV1, the volume that has been exhaled after the first second of forced expiration) on maximal oxygen consumption have been observed in several cross-sectional and longitudinal studies. Complex interactions between aging-related cellular and molecular processes affecting the lung, and structural and functional deterioration of the cardiovascular and respiratory systems account for the concomitant decline in pulmonary function and maximal oxygen consumption. Consequently, if long-term regular physical activity mitigates some of the aging-related decline in pulmonary function (i.e., FEV1 decline), this could also prevent a steep fall in maximal oxygen consumption. In contrast to earlier research findings, recent large-scale longitudinal studies provide growing evidence for the beneficial effects of physical activity on FEV1. Although further confirmation of those effects is required, these findings provide powerful arguments to start and/or maintain regular physical activity.

Comparison of heart rates at fixed percentages and the ventilatory thresholds in patients with interstitial lung disease.

Heart rate (HR) responses to maximal exercise are commonly used for the prescription of training intensities in pulmonary rehabilitation. Those intensities are usually based on fixed percentages of peak HR (HRpeak), heart rate reserve (HRR), or peak work load (Wpeak), and rarely on HRs at the individual ventilatory thresholds (VT1 and VT2) derived from cardiopulmonary exercise testing (CPET). For patients suffering from interstitial lung disease (ILD), data on cardiorespiratory responses to CPET are scarce. Thus, the aim of this study was to record cardiorespiratory responses to CPET and to compare fixed HR percentages with HRs at VT1 and VT2 in ILD patients. A total of 120 subjects, 80 ILD patients and 40 healthy controls, underwent a symptom-limited CPET. From the ILD patient, 32 suffered from idiopathic pulmonary fibrosis (IPF), 37 from connective tissue disease (CTD), and 11 from sarcoidosis. HRs at fixed percentages, that is, at 70%HRpeak, at 70%Wpeak, and at 60%HRR were significantly lower in the ILD patients compared with the control group (p-values: 0.001, 0.044, and 0.011). Large percentages of HR values at 70%Wpeak and 60%HRR ranged between the HRs at VT1 and VT2 in ILD subgroups and controls as well. HRs at 70%HRpeak were lower than HRs at VT1 in 66% of the IPF patients, 54% of the CTD patients, and 55% of patients with sarcoidosis compared with 18% in the control group. Our findings demonstrate a considerable scattering of fixed HR percentages compared with HRs at the individual VTs derived from CPET in ILD patients. These findings may provide valuable information for the prescription of exercise intensity in pulmonary rehabilitation of ILD patients.

[Masterplan 2025 of the Austrian Society of Pneumology (ASP)-the expected burden and management of respiratory diseases in Austria]. / Masterplan 2025 der Österreichischen Gesellschaft für Pneumologie (ÖGP) ­ die erwartete Entwicklung und Versorgung respiratorischer Erkrankungen in Österreich.

Scientific Members of the Austrian Society of Pneumology describe the expected development in respiratory health and provide guidance towards patient-oriented and cost-efficient respiratory care in Austria.Methods: In November 2017, respiratory care providers (physicians, nurses, physiotherapists) together with patient's advocacy groups and experts in health development, collaborated in workshops on: respiratory health and the environment, bronchial asthma and allergy, COPD, pediatric respiratory disease, respiratory infections, sleep disorders, interventional pneumology, thoracic oncology and orphan diseases.Results: Respiratory disease is extremely prevalent and driven by ill-health behavior, i.e. cigarette smoking, over-eating and physical inactivity. For the majority of respiratory diseases increased prevalence, but decreased hospitalizations are expected.The following measures should be implemented to deal with future challenges:1. Screening and case-finding should be implemented for lung cancer and COPD.2. E-health solutions (telemedicine, personal apps) should be used to facilitate patient management.3. Regional differences in respiratory care should be reduced through E­health and harmonization of health insurance benefits across Austria.4. Patient education and awareness, to reduce respiratory health illiteracy should be increased, which is essential for sleep disorders but relevant also for other respiratory diseases.5. Respiratory care should be inter-professional, provided via disease-specific boards beyond lung cancer (for ILDs, sleep, allergy)6. Programs for outpatient's pulmonary rehabilitation can have a major impact on respiratory health.7. Increased understanding of molecular pathways will drive personalized medicine, targeted therapy (for asthma, lung cancer) and subsequently health care costs.

Dose-dependent effects of omega-3-polyunsaturated fatty acids on systolic left ventricular function, endothelial function, and markers of inflammation in chronic heart failure of nonischemic origin: a double-blind, placebo-controlled, 3-arm study.

BACKGROUND: Supplementation with 1 g/d omega-3-polyunsaturated fatty acids (n3-PUFAs) demonstrated a small survival advantage in patients with chronic heart failure (CHF) in the GISSI-HF trial. However, a dose-efficacy relationship was postulated for the beneficial effects of n3-PUFA before. Therefore, we evaluated dose-dependent effects of n3-PUFA in patients with severe CHF. METHODS: In a double-blind, randomized, controlled pilot trial, 43 patients with severe, nonischemic heart failure received 1 g/d n3-PUFA (n = 14), 4 g/d n3-PUFA (n = 13), or placebo (n = 16) for 3 months. Changes in left ventricular ejection fraction (LVEF), flow-mediated vasodilation, plasma high-sensitive interleukin 6 and high-sensitive tumor necrosis factor α, and exercise peak oxygen consumption were assessed. RESULTS: Left ventricular ejection fraction increased in a dose-dependent manner (P = .01 for linear trend) in the 4 (baseline vs 3 months [mean ± SD]: 24% ± 7% vs 29% ± 8%, P = .005) and 1 g/d treatment groups (24% ± 8% vs 27% ± 8%, P = .02). Flow-mediated vasodilation increased significantly with high-dose 4 g/d n3-PUFA (8.4% ± 4.8% vs 11.6% ± 7.0%, P = .01) but only trendwise with low-dose 1 g/d (8.3% ± 5.3% vs 10.2% ± 4.3%, P = .07). Interleukin 6 significantly decreased with 4 g/d n3-PUFA (3.0 ± 2.9 pg/mL vs 0.7 ± 0.8 pg/mL, P = .03) but only trendwise with 1 g/d (4.5 ± 6.6 pg/mL to 1.6 ± 2.1 pg/mL, P = .1). High-sensitive tumor necrosis factor α decreased trendwise with 4 g/d n3-PUFA but remained unchanged with 1 g/d. In patients with maximal exercise effort, only 4 g/d increased the peak oxygen consumption. No changes in any investigated parameters were noted with placebo. CONCLUSION: Treatment with n3-PUFA for 3 months exerts a dose-dependent increase of LVEF in patients with CHF. In parallel, a significant improvement of endothelial function and decrease of interleukin 6 is found with high-dose n3-PUFA intervention.

Sirolimus in renal transplant recipients with tuberous sclerosis complex: clinical effectiveness and implications for innate immunity.

Tuberous sclerosis complex (TSC) is caused by constitutively activated mammalian target of rapamycin (mTOR) resulting in nonmalignant tumours of several organs and consequently renal failure. Recent reports suggest a possible beneficial role of the mTOR-inhibitor (mTOR-I) sirolimus for TSC; however, safety and efficiency of sirolimus in TSC patients after renal transplantation, both as primary immunosuppressant as well as anti-proliferative agent, are still undefined. Moreover, it is currently unknown whether the TSC mutation affects the primary immune response in these patients. In this article, we report on three TSC patients after renal transplantation who have been converted from a calcineurin-inhibitor (CNI)-based immunosuppression to sirolimus. During 2 years of follow-up, renal allograft function was stable or even improved, and no significant sirolimus-associated side-effects were noted. Beneficial effects of sirolimus against TSC were detected in the skin, along with improved spirometric measurements and an arrest of astrocytoma progression. We show that the inflammatory immune response was significantly altered in TSC patients as compared with controls and sirolimus potently affected both inflammatory cytokine production and vascular endothelial growth factor levels in these patients. Larger studies are warranted to further examine the relationship between clinical parameters and the molecular response to mTOR-inhibition in TSC patients after renal transplantation.

Vasoactive intestinal peptide (VIP) receptor expression in monocyte-derived macrophages from COPD patients.

Vasoactive intestinal peptide (VIP) is one of the most abundant molecules found in the respiratory tract. Due to its anti-inflammatory and bronchodilatatory properties, it has been proposed as a novel treatment for chronic obstructive pulmonary disease (COPD). The actions of VIP are mediated via three different G-protein-coupled receptors (VPAC1, VPAC2 and PAC1) which are expressed in the respiratory tract and on immunocompetent cells including macrophages. Alveolar macrophages (AM) are key players in the pathogenesis of COPD and contribute to the severity and progression of the disease. While VPAC1 has been reported to be elevated in subepithelial cells in smokers with chronic bronchitis, little is known about VPAC expression of AM in COPD patients. AM from COPD patients show a strong VPAC1 expression which exceeds VPAC2. A similar receptor expression pattern was also observed in lipopolysaccharide (LPS)-activated monocyte-derived macrophages (MDM) from healthy volunteers and COPD patients. VIP has been shown to down-regulate interleukin 8 (IL-8) secretion significantly in MDM after LPS stimulation. The response to VIP was similar in MDM from COPD patients and healthy volunteers. Our results indicate that VPAC1 up-regulation in macrophages is a common mechanism in response to acute and chronic pro-inflammatory stimuli. Although VPAC1 up-regulation is dominant, both receptor subtypes are necessary for optimal anti-inflammatory signaling. The high VPAC1 expression in AM may reflect the chronic pro-inflammatory environment found in the lung of COPD patients. Treatment with VIP may help to decrease the chronic inflammation in the lung of COPD patients.

Vasoactive intestinal peptide as a new drug for treatment of primary pulmonary hypertension.

Primary pulmonary hypertension is a fatal disease causing progressive right heart failure within 3 years after diagnosis. We describe a new concept for treatment of the disease using vasoactive intestinal peptide, a neuropeptide primarily functioning as a neurotransmitter that acts as a potent systemic and pulmonary vasodilator. Our rationale is based on the finding of a deficiency of the peptide in serum and lung tissue of patients with primary pulmonary hypertension, as evidenced by radioimmunoassay and immunohistochemistry. The relevance of this finding is underlined by an upregulation of corresponding receptor sites as shown by Northern blot analysis, Western blot analysis, and immunological techniques. Consequently, the substitution with the hormone results in substantial improvement of hemodynamic and prognostic parameters of the disease without side effects. It decreased the mean pulmonary artery pressure in our eight study patients, increased cardiac output, and mixed venous oxygen saturation. Our data provide enough proof for further investigation of vasoactive intestinal peptide and its role in primary pulmonary hypertension.