"Nitrogen Wash-Out" in Non-Hypoxaemic Patients with Spontaneous Pneumothorax: A Narrative Review.

Following current guidelines, spontaneous pneumothorax should be primarily managed with minimal invasive strategies. In real-world clinical practice, oxygen supplementation regardless of the presence or absence of hypoxemia is frequently applied in patients with a pneumothorax, with the intention to enhance the resorption rate of air from the pleural cavity ("nitrogen wash-out theory"). This review provides an overview of the scientific origin of this practice in animal models, and its clinical use in adult and paediatric patients. Clinical studies from PubMed, Embase and Cochrane library were reviewed by the authors using the keywords, "oxygen AND pneumothorax", "nitrogen washout AND pneumothorax" and "nitrogen AND pneumothorax", and recommendations from current guidelines were also reviewed by the authors. A selected total of nine clinical studies and three guidelines were included. Though in animal models there appears to be a therapeutic effect of oxygen therapy for the treatment of pneumothorax, clinical data in patient populations mainly stem from retrospective studies, mostly with a small sample size and inadequate study design. We recommend conducting prospective clinical studies with adequate methodology to address the question of whether or not oxygen therapy should be used to treat pneumothorax, regardless of the presence or absence of hypoxemia.

Effect of intravenous ferric carboxymaltose on exercise capacity and quality of life in patients with COPD : A pilot study.

BACKGROUND AND OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is associated with reduced exercise capacity. In COPD iron deficiency is found in up to 50% of patients and may impair exercise capacity, the potential therapeutic effect is yet unknown. We aimed to estimate the beneficial effect of intravenous ferric carboxymaltose on exercise capacity and quality of life in patients with COPD. METHODS: In this non-randomized, interrupted time series pilot trial we enrolled outpatients with stable COPD (GOLD II and III) and nonanemic iron deficiency (i.e., ferritin level < 100 µg/l or ferritin level 100-300 µg/l if transferrin saturation < 20%). Patients with cardiovascular-or inflammatory diseases were excluded. Participants performed 6­minute walking test (6-MWT) and cardiopulmonary exercise testing (CPET) and completed the St. George's Respiratory Questionnaire (SGRQ). RESULTS: From 35 screened patients, 11 (72% male, 63 ± 8 years, FEV1%predicted 44 ± 14) were included. Mean ferritin and hemoglobin were 70 ± 41 µg/l and 13.8 ± 1.7 g/dl, respectively. Four weeks after iron administration the 6­MWT distance increased by 34.7 ± 34.4 m (95% CI, 10.0-59.3); p = 0.011. The VO2max increased by 1.87 ± 1.2 ml/kg/min (95% CI, 0.76-3); p = 0.006. Mean score of SGRQ was reduced by 7.56 ± 6.12 units (95% CI, 3 to 11); p = 0.004. The insignificant alteration in hemoglobin did not correlate with increase in exercise capacity. CONCLUSION: Administration of intravenous iron was associated with improved exercise capacity and quality of life in stable COPD patients independent of hemoglobin. Our data provide a basis to calculate a statistically sufficient sample size for a randomized controlled follow-up study.

Effects of Dynamic Hyperinflation on Left Ventricular Diastolic Function in Healthy Subjects - A Randomized Controlled Crossover Trial.

Objective: Diastolic dysfunction of the left ventricle is common in patients with chronic obstructive pulmonary disease (COPD). Dynamic hyperinflation has been suggested as a key determinant of reduced diastolic function in COPD. We aimed to investigate the effects of induced dynamic hyperinflation on left ventricular diastolic function in healthy subjects to exclude other confounding mechanisms associated with COPD. Design: In this randomized controlled crossover trial (NCT03500822, https://www.clinicaltrials.gov/), we induced dynamic hyperinflation using the validated method of expiratory resistance breathing (ERB), which combines tachypnea with expiratory resistance, and compared the results to those of tachypnea alone. Healthy male subjects (n = 14) were randomly assigned to the ERB or control group with subsequent crossover. Mild, moderate, and severe hyperinflation (i.e., ERB1, ERB2, ERB3) were confirmed by intrinsic positive end-expiratory pressure (PEEPi) using an esophageal balloon catheter. The effects on diastolic function of the left ventricle were measured by transthoracic echocardiographic assessment of the heart rate-adjusted transmitral E/A-ratio and E/e'-ratio. Results: We randomly assigned seven participants to the ERB group and seven to the control group (age 26 [24-26] vs. 24 [24-34], p = 0.81). Severe hyperinflation decreased the E/A-ratio compared to the control condition (1.63 [1.49-1.77] vs. 1.85 [0.95-2.75], p = 0.039), and moderate and severe ERB significantly increased the septal E/e'-ratio. No changes in diastolic function were found during mild hyperinflation. PEEPi levels during ERB were inversely correlated with the E/A ratio (regression coefficient = -0.007, p = 0.001). Conclusions: Our data indicate dynamic hyperinflation as a determinant of left ventricular diastolic dysfunction in healthy subjects. Therapeutic reduction of hyperinflation might be a treatable trait to improve diastolic function in patients with COPD.

Induction of dynamic hyperinflation by expiratory resistance breathing in healthy subjects - an efficacy and safety study.

NEW FINDINGS: What is the central question of this study? The study aimed to establish a novel model to study the chronic obstructive pulmonary disease (COPD)-related cardiopulmonary effects of dynamic hyperinflation in healthy subjects. What is the main finding and its importance? A model of expiratory resistance breathing (ERB) was established in which dynamic hyperinflation was induced in healthy subjects, expressed both by lung volumes and intrathoracic pressures. ERB outperformed existing methods and represents an efficacious model to study cardiopulmonary mechanics of dynamic hyperinflation without potentially confounding factors as present in COPD. ABSTRACT: Dynamic hyperinflation (DH) determines symptoms and prognosis of chronic obstructive pulmonary disease (COPD). The induction of DH is used to study cardiopulmonary mechanics in healthy subjects without COPD-related confounders like inflammation, hypoxic vasoconstriction and rarefication of pulmonary vasculature. Metronome-paced tachypnoea (MPT) has proven effective in inducing DH in healthy subjects, but does not account for airflow limitation. We aimed to establish a novel model incorporating airflow limitation by combining tachypnoea with an expiratory airway stenosis. We investigated this expiratory resistance breathing (ERB) model in 14 healthy subjects using different stenosis diameters to assess a dose-response relationship. Via cross-over design, we compared ERB to MPT in a random sequence. DH was quantified by inspiratory capacity (IC, litres) and intrinsic positive end-expiratory pressure (PEEPi, cmH2 O). ERB induced a stepwise decreasing IC (means (95% CI): tidal breathing: 3.66 (3.45-3.88), ERB 3 mm: 3.33 (1.75-4.91), 2 mm: 2.05 (0.76-3.34), 1.5 mm: 0.73 (0.12-1.58) litres) and increasing PEEPi (tidal breathing: 0.70 (0.50-0.80), ERB 3 mm: 11.1 (7.0-15.2), 2 mm: 22.3 (17.1-27.6), 1.5 mm: 33.4 (3.40-63) cmH2 O). All three MPT patterns increased PEEPi, but to a far lesser extent than ERB. No adverse events during ERB were noted. In conclusion, ERB was proven to be a safe and efficacious model for the induction of DH and might be used for the investigation of cardiopulmonary interaction in healthy subjects.

Homeopathic Treatment as an Add-On Therapy May Improve Quality of Life and Prolong Survival in Patients with Non-Small Cell Lung Cancer: A Prospective, Randomized, Placebo-Controlled, Double-Blind, Three-Arm, Multicenter Study.

LESSONS LEARNED: Conventional medicine and homeopathy work well together. Quality of life improves with additive homeopathy in patients with non-small cell lung cancer (NSCLC). Survival improves with additive homeopathy in patients with NSCLC. BACKGROUND: Patients with advanced non-small cell lung cancer (NSCLC) have limited treatment options. Alongside conventional anticancer treatment, additive homeopathy might help to alleviate side effects of conventional therapy. The aim of the present study was to investigate whether additive homeopathy might influence quality of life (QoL) and survival in patients with NSCLC. METHODS: In this prospective, randomized, placebo-controlled, double-blind, three-arm, multicenter, phase III study, we evaluated the possible effects of additive homeopathic treatment compared with placebo in patients with stage IV NSCLC, with respect to QoL in the two randomized groups and survival time in all three groups. Treated patients visited the outpatients' centers every 9 weeks: 150 patients with stage IV NSCLC were included in the study; 98 received either individualized homeopathic remedies (n = 51) or placebo (n = 47) in a double-blinded fashion; and 52 control patients without any homeopathic treatment were observed for survival only. The constituents of the different homeopathic remedies were mainly of plant, mineral, or animal origin. The remedies were manufactured by stepwise dilution and succussion, thereby preparing stable Good Manufacturing Practice grade formulations. RESULTS: QoL as well as functional and symptom scales showed significant improvement in the homeopathy group when compared with placebo after 9 and 18 weeks of homeopathic treatment (p < .001). Median survival time was significantly longer in the homeopathy group (435 days) versus placebo (257 days; p = .010) as well as versus control (228 days; p < .001). Survival rate in the homeopathy group differed significantly from placebo (p = .020) and from control (p < .001). CONCLUSION: QoL improved significantly in the homeopathy group compared with placebo. In addition, survival was significantly longer in the homeopathy group versus placebo and control. A higher QoL might have contributed to the prolonged survival. The study suggests that homeopathy positively influences not only QoL but also survival. Further studies including other tumor entities are warranted.