An overview of efficacy and safety of ambroxol for the treatment of acute and chronic respiratory diseases with a special regard to children.

Introduction: Ambroxol (2-amino-3,5-dibromo-N-[trans-4-hydroxycyclohexyl]benzylamine), an over-the-counter product, is a mucoactive agent and has been used widely to treat both acute and chronic respiratory diseases since 1978. This review aims to provide an overview of the clinical evidence available on the use of ambroxol in children with acute and chronic respiratory diseases. Data for this review were obtained from both published and unpublished clinical studies, and real-world evidence studies. Although conducted prior to the introduction of Good Clinical Practice (GCP), these studies, representing almost 1,300 pediatric patients, report strong clinical outcomes following the use of ambroxol in pediatric patients. Furthermore, efficacy findings were consistent irrespective of age, including for patients as young as 1 month old. Additionally, the majority of studies found ambroxol to be well tolerated in children. Taken together, the clinical evidence for ambroxol shows treatment effects that offer significant benefits to pediatric patients for its licensed use as a secretolytic therapy in acute and chronic bronchopulmonary disorders associated with abnormal mucus secretion and impaired mucus transport. The findings from this review indicate that ambroxol, for its intended over-the-counter indications, is both efficacious and well tolerated in children and that the favorable benefit/risk profile of ambroxol reported in adults extends to the pediatric population, starting from early infancy, with acute and chronic respiratory diseases.

Safety of ambroxol in the treatment of airway diseases in adult patients.

INTRODUCTION: Ambroxol is a widely used secretolytic and mucoactive over-the-counter agent primarily used to treat respiratory diseases associated with viscid mucus. Following post-marketing reports of hypersensitivity reactions and severe cutaneous adverse reactions (SCARs) possibly linked to ambroxol, the European Union's Pharmacovigilance Risk Assessment Committee (PRAC) initiated in April 2014 a review of the safety of ambroxol in all its registered indications, which was finalized in 2016. Areas covered: Here, we evaluate the clinical safety of ambroxol and provide an expert opinion on the benefit-risk balance of ambroxol in the treatment of adult patients with bronchopulmonary diseases. The evidence for this review is derived from clinical trials of ambroxol that were provided to the PRAC by the marketing authorization holders of ambroxol-containing medicines. Expert opinion: Clinical experience accumulated from randomized clinical trials and observational studies suggests that ambroxol is a safe and well-tolerated treatment of bronchopulmonary diseases, with a well-balanced and favorable benefit-risk profile. All reported adverse events were mild and self-limiting, and the risk of SCARs with ambroxol is low. Further investigations could address the safety and efficacy of ambroxol in pediatric lung diseases and in additional therapeutic indications, such as biofilm-dependent airway disease and lysosomal storage disorders.

The effect on snoring of using a pillow to change the head position.

PURPOSE: Although not a disease, primary snoring often leads to social problems. In an earlier retrospective pilot study, we found hints that individuals were snoring less in a lateral versus a supine head position. The aim of this study is to elucidate on the effect of an anti-snoring pillow which changes the head position. METHODS: We designed an interventional, controlled, and randomized crossover study. It included 22 participants, between 18 and 78 years, who snored, had a BMI ≤ 30, and a sleep partner. Obstructive sleep apnea was ruled out by polysomnography (PSG) or by respiratory polygraphy (PG). Two potential participants dropped out. The first two phases were done at home (4 weeks in total), followed by two nights of polysomnography in our sleep laboratory. During all phases, questionnaires regarding snoring, sleep quality, and pillow tolerance were completed by the patients and, as relevant, by their partners. RESULTS: The PSG parameters revealed a significant reduction in the snoring index (p = 0.03) when on the activated pillow without a deterioration in other respiratory parameters. This correlated well with the visual analog scale (VAS) that showed a significant decrease in snoring with the activated pillow according to the bed partners (p < 0.001). Subjective acceptance of the pillow during the study period was 100%. CONCLUSIONS: This study shows that by using a pillow to change the head position, it is possible to reduce both subjective and objective snoring severity. GERMAN CLINICAL TRIAL NUMBER: DRKS 00008744 AND ETHICS COMMISSION REGISTRY NUMBER REGISTRY NUMBER 2013-406 M-MA.

[Using a Standardized Questionnaire for Coagulation Assessment in Children Undergoing Tonsillectomy]. / Standardisierte Gerinnungsanamnese vor Tonsillektomie und Adenotomie im Kindesalter.

Introduction A 2006 position paper suggests assessing coagulation status via a standardized questionnaire instead of performing routine coagulation testing for children undergoing tonsillectomy/adenotomy. The aim of the presented study was to evaluate whether this paradigm change led to a change in the incidence of secondary bleeding. Methods Descriptive statistical analysis of existing clinical data was performed to evaluate the incidence and characteristics of secondary bleeding in children after tonsillectomy/adenotomy in 2003 vs. 2009. Result In 2003, 352 children underwent surgery. Secondary bleeding occurred in 25 cases (7.1%), 18, (6.1%) of which required surgical treatment. In 2009, 20 out of 293 children who had undergone tonsillectomy/adenotomy suffered from secondary bleeding, 14 required (4.7%) surgical treatment. There was no significant difference in the incidence of bleeding between those years. In 5 children who suffered from secondary bleeding in 2003, preoperative diagnostic blood coagulation testing was performed, none of them showed abnormal results. Furthermore, none of the diagnostic blood coagulation tests performed after secondary bleeding in both groups showed any abnormalities. Conclusion Using a standardized questionnaire instead of a diagnostic blood coagulation testing for preoperative coagulation assessment does not have an influence on the incidence of secondary bleeding after tonsillectomy/adenotomy. The results of this study suggest that secondary bleeding is not is not caused by abnormal hemostasis.

Adjuvants for immunotherapy.

PURPOSE OF REVIEW: This article gives an overview about the current state of preclinical and clinical studies using different kinds of adjuvants and their effect on allergen-specific immunotherapy (SIT). RECENT FINDINGS: Recently, vectors such as liposomes and microspheres and adjuvants such as Toll-like-receptor agonists [e.g. nonmethylated cytosine-guanine dinucleotide (CpG) motifs derived from bacterial DNA or monophosphoryl lipid A (MPL A)] have been used in clinical phase II and III trials demonstrating encouraging clinical effects. SUMMARY: SIT has been optimized for more than 100 years with different approaches. Among these, adjuvants have been shown to amplify the effect of SIT by modulating the immune response to this therapy. In the first part, this article reviews the immunological mechanisms underlying the use of adjuvants targeting key cells of the innate immune system such as dendritic cells. In the second part, it overviews first clinical trials which have been reported so far in both subcutaneous and sublingual allergen-specific immunotherapy investigating the therapeutic potential of adjuvanted extracts. Most of these clinical trials revealed both clinical efficacy and immunological effects. However, more studies are warranted to further focus the specific role of adjuvants in the process of tolerance induction in allergic patients.