A detailed analysis of possible efficacy signals of NTHi-Mcat vaccine against severe COPD exacerbations in a previously reported randomised phase 2b trial.

BACKGROUND: An investigational vaccine containing non-typeable Haemophilus influenzae (NTHi) and Moraxella catarrhalis (Mcat) surface proteins did not show vaccine efficacy (VE) against combined moderate and severe (moderate/severe) exacerbations in a randomised, observer-blinded, placebo-controlled phase 2b trial of patients with chronic obstructive pulmonary disease (COPD). Nevertheless, observations on rates of severe exacerbations and hospitalisations encouraged further evaluation. METHODS: Patients with stable COPD (moderate to very severe airflow limitation, Global Initiative for Chronic Obstructive Lung Disease [GOLD] stage 2-4), 40-80 years and at least one moderate/severe exacerbation in the last year received two doses of NTHi-Mcat vaccine or placebo plus standard care. Secondary analyses were conducted on VE against exacerbations according to severity. Potential predictive factors at baseline for VE against severe exacerbations were explored in post-hoc analyses. RESULTS: Of 606 patients enrolled, 571 were included in the efficacy analysis (279 in NTHi-Mcat vaccine group, 292 in placebo group). VE against severe acute exacerbations of COPD (AECOPD) in various subgroups was 52.11 % (p = 0.015; frequent exacerbators), 65.43 % (p = 0.015; baseline GOLD grade 4), 38.24 % (p = 0.034; previous pneumococcal and/or influenza vaccination). VE was 52.49 % (p = 0.044) for the 6-12 months period after 1 month post-dose 2. Multivariable analysis identified two factors (frequent exacerbator status plus inhaled corticosteroid use at baseline) associated with significant VE against severe AECOPD; in this subpopulation, VE was 74.99 % (p < 0.001). CONCLUSION: Results suggest potential efficacy with the NTHi-Mcat vaccine against severe exacerbations in certain patients with COPD, in particular those who have frequent exacerbations and use inhaled corticosteroids. This potential signal requires confirmation in an appropriately designed prospective clinical trial. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03281876.

Effect of inhaled budesonide/formoterol fumarate dihydrate delivered via two different devices on lung function in patients with COPD and low peak inspiratory flow.

BACKGROUND AND AIMS: Low peak inspiratory flow (PIF) is common following severe exacerbations of chronic obstructive pulmonary disease (COPD). Patients with COPD and low PIF may be at risk of suboptimal delivery of inhaled therapies to the airways, especially when using devices such as dry powder inhalers (DPIs), which require greater inspiratory effort than metered dose inhalers (MDIs). We report the results from a 2-week crossover study evaluating the effects of inhaled dual therapy with budesonide/formoterol fumarate dihydrate with an MDI with a spacer versus a DPI in patients with COPD and low PIF. METHODS: This randomized, open-label, two-period (each 1 week in duration) crossover efficacy and safety study included patients with severe-to-very severe COPD and PIF < 50 L/min (NCT04078126). Patients were randomized 1:1 to twice-daily budesonide/formoterol fumarate dihydrate MDI (BFF MDI) 320/10 µg with a spacer for 1 week followed by twice-daily budesonide/formoterol fumarate dihydrate DPI (BUD/FORM DPI) 320/9 µg for 1 week, or the inverse. The primary endpoint was peak change from baseline in forced expiratory volume in 1 s (FEV1) within 4 h post-dose following 1 week of treatment. Other assessments included pre-dose lung function, pharmacokinetics, and safety, as assessed by adverse events. RESULTS: The modified intention-to-treat analysis set comprised 30 patients (mean age: 66.9 years; mean baseline FEV1: 766 mL; mean COPD assessment test score: 22.20). Following 1 week of treatment, both BFF MDI and BUD/FORM DPI improved mean [95% confidence interval (CI)] peak FEV1 4 h post-dose [256 (190, 322) mL and 274 (208, 340) mL, respectively]. No clinically meaningful difference between treatments was observed for any lung function endpoint. There were no unexpected safety findings. CONCLUSION: Dual therapy with BFF MDI and with BUD/FORM DPI led to improvements in lung function in patients with severe-to-very severe COPD and low PIF.

Unusual allergen in a butcher with respiratory symptoms.

A 37-year-old butcher developed respiratory symptoms during sausage and chicken production in a large company. In addition to various spices, the enzyme transglutaminase was a possible cause. The lung function test showed mild partial reversible airway obstruction and severe bronchial hyperresponsiveness. The IgE test showed sensitizations to various spice mixtures, coriander (0.74 kU/L), and to the ImmunoCAP-bound transglutaminase preparation from the workplace (7.12 kU/L). The skin prick tests with this transglutaminase were also positive. In the immunoblot of this preparation, a 40-kD protein reacted with the patient's IgE and was identified as transglutaminase from Streptomyces mobaraensis by inhibition experiments. This is the first case of a butcher with an allergy to transglutaminase. After moving to a small enterprise without enzyme use, his symptoms improved. Sensitization and the course of the symptoms indicate a dominant role of transglutaminase in the patient's allergic asthma.

Understanding Dry Powder Inhalers: Key Technical and Patient Preference Attributes.

Inhalable medications for patients with asthma and chronic obstructive pulmonary disease (COPD) can be confusing even for health care professionals because of the multitude of available devices each with different operating principles. Dry powder inhalers (DPI) are a valuable option for almost all of the patients with asthma or COPD. Based on recorded patient inspiratory profiles, the peak inspiratory flow requirement of 30 L min-1 of high-resistance devices does not usually pose any practical limitations for the patients. Suboptimal adherence and errors in device handling are common and require continuous checking and patient education in order to avoid these pitfalls of all inhalation therapy. The aim of this opinion paper is to describe the working principles of DPIs and to summarise their key properties in order to help prescribing the correct inhaler for each patient.Funding: Orion Pharma.

Insights from the German Compassionate Use Program of Nintedanib for the Treatment of Idiopathic Pulmonary Fibrosis.

BACKGROUND: Nintedanib is approved for the treatment of idiopathic pulmonary fibrosis (IPF) and has been shown to slow disease progression by reducing annual lung function decline. OBJECTIVE: To evaluate the results of a large cohort of IPF patients treated with nintedanib within a compassionate use program (CUP) in Germany (9 centers). METHODS: Patients (≥40 years) were required to have a confirmed diagnosis of IPF, a forced vital capacity (FVC) ≥50% predicted (pred.) and a carbon monoxide diffusing capacity (DLCO) 30-79% pred. and not to be eligible for pirfenidone treatment. Clinical data, pulmonary function tests and adverse events were recorded up to July 2015. RESULTS: Sixty-two patients (48 male/14 female) with moderate IPF (FVC 64 ± 17% pred. and DLCO 40 ± 10% pred.) were treated with nintedanib. 77% of patients switched from pirfenidone (mean treatment duration 14 ± 2 months) mostly due to disease progression (mean decline in FVC 7.4 ± 3% pred. in the 6 months prior to nintedanib intake). Initiation of nintedanib treatment occurred 69 ± 29 months after IPF diagnosis, and mean treatment duration was 8 ± 4 months. Most patients (63%) stabilized 6 months after treatment start (mean FVC decline 3 ± 1 vs. -17 ± 2% in patients with disease progression; p < 0.01). The most common adverse events were diarrhea (63%) and weight loss (50%). Dose reduction occurred in 34% of cases and treatment discontinuation in 10%. CONCLUSION: Nintedanib treatment was generally well tolerated and was associated with FVC stabilization in the majority of IPF patients in this CUP setting where most patients were not treatment naïve. Our data are in agreement with the previously published data.

[Inpatient treatment for CRPS I by use of complementary medicine]. / Stationare, naturheilkundliche Therapie eines komplexen regionalen Schmerzsyndroms (CRPS I).

INTRODUCTION: Complex regional pain syndromes (CRPS) are mainly characterized by a burning, intense spontaneous pain,mechanical allodynia of the affected limb, disorders of the skin,local hyperhidrosis, lymphedema as well as trophic disorders of the skin, bones and joints. The overall clinical appearance is dominated by a dysfunction of the sympathetic nervous system. One dominant etiological hypothesis is that major mechanisms for CRPS symptoms, which might be present during the course of CRPS, are trauma-related cytokine release, exaggerated neurogenic inflammation, sympathetically maintained pain, and cortical reorganization in response to chronic pain. CASE REPORT: We report the case of a 33-year-old female patient who suffered from a CRPS type I (cold type) of the left foot which had been traumatically induced 9 months before. The patient presented with a severe pain syndrome, an allodynia of the dermatomes L5 and S1 left with significant trophic skin disturbances, followed by a lymphedema and a malposition (pronation) of the left dorsum pedis. METHODS: In the course of a 10-week in-house treatment the patient received a multidisciplinary therapy-management based on complementary medicine with intensive use of hydrotherapy according to Kneipp, and physiotherapy. RESULTS: Pain intensity over treatment decreased from 8 (initial) to 2 (after 8 weeks) ona 10-point numeric rating scale. Furthermore, local symptoms of the left foot, i.e. hyperhidrosis, trophic skin disorders and lymphedema decreased significantly. CONCLUSIONS: Therapeutic strategies derived from complementary medicine may be an effective approach to the complex treatment of CRPS. Their effects should be further investigated in controlled clinical trials.