Changes in pharmacist's recommendations of over-the-counter treatments for the common cold during the COVID-19 pandemic.

BACKGROUND: The common cold is one of the most frequently occurring illnesses worldwide. The aim of this study was to determine which OTC anti-common cold medications were most often recommended by pharmacists and if the COVID-19 pandemic affected such recommendations. METHODS: Non-interventional, observational research trial using a self-developed questionnaire to collect data on pharmacists' recommendations for anti-common cold OTC treatment. The data were collected during the COVID-19 pandemic (December 2021-February 2022) in four large community network pharmacies in Lodz (Poland) and then compared with an analogue period of time before the pandemic (December 2019-February 2020). RESULTS: During COVID-19 pandemic there was a significant (p < 0.05) reduction in paracetamol, acetylsalicylic acid, metamizole magnesium, inosines, alpha-mimetics, mucolytics, homeopathics, and sore throat products and an increase in other tablets/capsules and add-on product recommendations. There was a significant relationship (p < 0.05, OR > 1) between the recommended frequency of paracetamol, inosines, sore throat products (each symptom), metamizole magnesium (headache, fever), acetylsalicylic acid (headache, fever, fatigue), NSAIDs, alpha-mimetics (headache, rhinorrhea), pseudoephedrine (rhinorrhea), homeopathics (headache), herbal products (fatigue), antihistamines (rhinorrhea, cough), and mucolytics (headache, fever, cough). CONCLUSIONS: Favorable prices (before COVID-19 pandemic) and reports on common NSAIDs side effects (beginning of the pandemic) led to high sale of paracetamol. Increased awareness of clinical effectiveness of some medications or their reduced availability influenced their limited recommendations.

[Evaluation of the efficacy and safety of a combination drug containing ambroxol, guaifenesin, and levosalbutamol versus a fixed-dose combination of bromhexine/guaifenesin/salbutamol in the treatment of productive cough in adult patients with acute bronchitis].

AIM: To evaluate the efficacy and safety of a combination drug containing ambroxol, guaifenesin, and levosalbutamol, oral solution, versus Ascoril Expectorant, syrup (combination of bromhexine, guaifenesin, and salbutamol) in the treatment of productive cough in adult patients with acute bronchitis. MATERIALS AND METHODS: This open-label, randomized, phase III study included patients with acute bronchitis who had a productive cough with difficulty in sputum expectoration. 244 patients were randomized in a 1:1 ratio and received 10 mL of the study drug or reference drug 3 times daily for 2 weeks. After 7 and 14 days of treatment, the physician evaluated patient's subjective complaints and the efficacy of therapy. The primary endpoint was the proportion of patients with high and very high efficacy. RESULTS: The primary endpoint was reached by 70 (0.5738) patients in the study drug group and 54 (0.4426) in the reference drug group (p=0.04). The intergroup difference was 0.1311 [95% confidence interval: 0.0057; 0.2566]. The lower limit of the 95% confidence interval was above zero, which confirms the superiority of therapy with the study drug over therapy with Ascoril Expectorant. The proportion of patients with a 1-point total score reduction and with complete resolution of all symptoms according to the Modified Cough Relief and Sputum Expectoration Questionnaire after 7 and 14 days was numerically higher in the study drug group versus the reference drug group. There were no statistically significant differences between the groups in the incidence of adverse events. CONCLUSION: The efficacy of a new combination drug containing ambroxol, guaifenesin, and levosalbutamol in the treatment of productive cough in adult patients with acute bronchitis is superior to the efficacy of Ascoril Expectorant. The safety profiles of the study drug and the reference drug were comparable.

Use of dornase alfa in pediatric patients without cystic fibrosis.

OBJECTIVES: Literature regarding clinical benefits of dornase alfa (DNase) in pediatric patients without cystic fibrosis is lacking. In December 2020, the study institution implemented restrictions to limit DNase use in this patient population. The primary objective was adherence to DNase ordering restrictions. Secondary objectives included length of stay, respiratory function, and use of inhaled mucolytic agents. METHODS: This single-center retrospective chart review included patients less than 18 years of age who received DNase one year prior to through one year after order restriction implementation. Data collected included patient demographics and respiratory clinical parameters. Dosing regimens for DNase, n-acetylcysteine, and hypertonic saline were collected, as well as changes in length of stay (LOS) and adherence to ordering restrictions. RESULTS: Of 101 total DNase orders, 45 were placed after implementation of ordering restrictions and 16 (36%) met all ordering criteria. Hospital and intensive care unit (ICU) LOS after implementation of restrictions were not significantly different (p = 0.767 and p = 0.219, respectively). There was no significant change in patients' mean oxygenation index (p = 0.252) or FiO2% (p = 0.113) 24 hours after DA administration. CONCLUSION: Respiratory function did not significantly change after DNase administration. Implementing restrictions on DNase did not impact intensive care unit or hospital LOS. Adherence to DNase ordering restrictions could be improved.

Mucolytics for acute exacerbations of chronic obstructive pulmonary disease: a meta-analysis.

This meta-analysis explored the safety and effectiveness of mucolytics as an add-on treatment for chronic obstructive pulmonary disease (COPD) exacerbations. Based on a pre-registered protocol and following Cochrane methods, we systematically searched for relevant randomised or quasi-randomised controlled trials (RCTs). We used the Risk of Bias v2 tool for appraising the studies and performed random-effect meta-analyses when appropriate. We assessed certainty of evidence using GRADE. This meta-analysis included 24 RCTs involving 2192 patients with COPD exacerbations, entailing at least some concerns of methodological bias. We demonstrated with moderate certainty that mucolytics increase the rate of treatment success (relative risk 1.37, 95% CI 1.08-1.73, n=383), while they also exert benefits on overall symptom scores (standardised mean difference 0.86, 95% CI 0.63-1.09, n=316), presence of cough at follow-up (relative risk 1.93, 95% CI 1.15-3.23) and ease of expectoration (relative risk 2.94, 95% CI 1.68-5.12). Furthermore, low or very low certainty evidence suggests mucolytics may also reduce future risk of exacerbations and improve health-related quality of life, but do not impact on breathlessness, length of hospital stay, indication for higher level of care or serious adverse events. Overall, mucolytics could be considered for COPD exacerbation management. These findings should be validated in further, rigorous RCTs.

An Elemental Diet Enriched in Amino Acids Alters the Gut Microbial Community and Prevents Colonic Mucus Degradation in Mice with Colitis.

The role of dietary amino acids or intact proteins in the progression of colitis remains controversial, and the mechanism involving gut microbes is unclear. Here, we investigated the effects of an elemental diet (ED) enriched in amino acids and a polymeric diet enriched in intact protein on the pathogenesis of dextran sulfate sodium (DSS)-induced colitis in mice. Our results showed that the ED induced remission of colitis in mice. Notably, ED treatment reduced the abundance of the mucolytic bacteria Akkermansia and Bacteroides, which was attributed to decreased colonic protein fermentation. Consistently, the activities of mucolytic enzymes were decreased, leading to protection against mucus layer degradation and microbial invasion. Fecal microbiota transplantation from ED-fed mice reshaped microbial ecology and alleviated intestinal inflammation in recipient mice. The ED failed to induce remission of colitis in pseudogermfree mice. Together, our results demonstrate the critical role of the gut microbiota in the prevention of colitis by an ED. IMPORTANCE The prevalence of inflammatory bowel disease is rapidly increasing and has become a global burden. Several specific amino acids have been shown to benefit mucosal healing and colitis remission. However, the role of amino acids or intact proteins in diets and enteral nutrition formulas is controversial, and the mechanisms involving gut microbes remain unclear. In this study, we investigated the effects of an elemental diet (ED) enriched in amino acids and a polymeric diet enriched in intact protein on the pathogenesis of colitis in mice. The underlying mechanisms were explored by utilizing fecal microbiota transplantation and pseudogermfree mice. ED treatment reduced the abundance of mucolytic bacteria, thereby protecting the mucus layer from microbial invasion and degradation. For the first time, we convincingly demonstrated the critical role of gut microbiota in the effects of the ED. This study may provide new insights into the gut microbiota-diet interaction and its role in human health.

Unintentional poisoning by cough and cold medications: Drugs with little usefulness and potential toxicity.

INTRODUCTION: The use of medications to relieve the symptoms of the "common cold" in children is very frequent. In addition to the lack of scientific evidence supporting its usefulness, there is evidence of potential toxicity, and serious and even fatal cases of intoxication have been described. The objective was to describe the clinical and epidemiological characteristics of the patients treated in a paediatric emergency department (PED) for suspected unintentional intoxication by a cold medicine. MATERIAL AND METHODS: Observational and analytical study of patients aged less than 18 years managed in a PED for suspected unintentional poisoning by a cold medicine between July 2012 and June 2020. We classified severity according to the Poisoning Severity Score (PSS): PSS-0 = no toxicity; PSS-1 = mild toxicity; PSS-2 = moderate; PSS-3 = severe; PSS-4 = lethal. If the intoxication occurred while the patient was in active treatment with the drug, we determined whether the patient's age was in the applicable range established in the therapeutic indications provided in the summary of product characteristics. RESULTS: The study included data for 63 cases. The drugs involved were decongestants and mucolytics (31; 49.2%), antitussives (26; 41.2%) and oral bronchodilators (6; 9.5%). The distribution by severity was 40 cases with PSS-0 (63.5%), 21 with PSS-1 (33.3%), 1 with PSS-2 (1.6%) and 1 with PSS-3 (1.6%). In 29 patients (46.0%) there was a history of therapeutic use; in 15 of these cases (51.7%) the age was lower than recommended in the summary of product characteristics. In 14 patients (22.2%) the intoxication was due to administration of the wrong dose by caregivers. CONCLUSION: Although scientific evidence does not support the use of cold medicines in children, unintentional intoxications by these drugs keep happening, in some cases causing moderate or severe symptoms.

Total flavonoids of Inula japonica alleviated the inflammatory response and oxidative stress in LPS-induced acute lung injury via inhibiting the sEH activity: Insights from lipid metabolomics.

BACKGROUND: Acute lung injury (ALI) is a severe respiratory disease characterized by diffuse lung interstitial and respiratory distress and pulmonary edema with a mortality rate of 35%-40%. Inula japonica Thunb., known as "Xuan Fu Hua" in Chinese, is a traditional Chinese medicine Inulae Flos to use for relieving cough, eliminating expectorant, and preventing bacterial infections in the clinic, and possesses an anti-pulmonary fibrosis effect. However, the effect and action mechanism of I. japonica on ALI is still unclear. PURPOSE: This study aimed to investigate the protective effect and underlying mechanism of total flavonoids of I. japonica (TFIJ) in the treatment of ALI. STUDY DESIGN AND METHODS: A mouse ALI model was established through administration of LPS by the intratracheal instillation. Protective effects of TFIJ in the inflammation and oxidative stress were studied in LPS-induced ALI mice based on inflammatory and oxidative stress factors, including MDA, MPO, SOD, and TNF-α. Lipid metabolomics, bioinformatics, Western blot, quantitative real-time PCR, and immunohistochemistry were performed to reveal the potential mechanism of TFIJ in the treatment of ALI. RESULTS: TFIJ significantly alleviated the interstitial infiltration of inflammatory cells and the collapse of the alveoli in LPS-induced ALI mice. Lipid metabolomics demonstrated that TFIJ could significantly affect the CYP2J/sEH-mediated arachidonic acid metabolism, such as 11,12-EET, 14,15-EET, 8,9-DHET, 11,12-DHET, and 14,15-DHET, revealing that sEH was the potential target of TFIJ, which was further supported by the recombinant sEH-mediated the substrate hydrolysis in vitro (IC50 = 1.18 µg/ml). Inhibition of sEH by TFIJ alleviated the inflammatory response and oxidative stress via the MAPK, NF-κB, and Nrf2 signaling pathways. CONCLUSION: These results demonstrated that TFIJ could suppress the sEH activity to stabilize the level of EETs, allowing the alleviation of the pathological course of lung injury in LPS-treated mice, which suggested that TFIJ could serve as the potential agents in the treatment of ALI.

Effects of Acylhydrazone Derivatives on Experimental Pulmonary Inflammation by Chemical Sensitization.

BACKGROUND: Chronic lung diseases are characterized by airway inflammation and remodelling of the lung parenchyma that triggers considerable impairment of respiratory function. OBJECTIVE: In this study, two compounds belonging to the N-acylhydrazone class were evaluated, aiming to identify new therapeutic agents for pulmonary inflammatory diseases. MATERIALS AND METHODS: The acute toxicity of 2-cyano-N'-(3-ethoxy-4-hydroxybenzylidene)- acetohydrazide (JR-12) and N'-benzylidene-2-cyano-3-phenylacrylohydrazide (JR09-Bz) was evaluated. Afterwards, they were tested in models of ovalbumin (OVA)-induced allergic asthma and pleurisy, bleomycin-induced pulmonary fibrosis, in addition to mucolytic activity. RESULTS AND DISCUSSION: The compounds did not show toxicity at the dose of 2,000 mg/kg, and no animal died. On OVA-induced pleurisy, animals treated with JR-12 or JR09-Bz at a dose of 10 mg/kg (orally) showed significant inhibition of the leukocyte infiltrate in the bronchoalveolar lavage by 62.5% and 61.5%, respectively, compared to the control group. The compounds JR-12 and JR09-Bz were also active in blocking the allergic asthmatic response triggered by OVA, reducing the leukocyte infiltrate by 73.1% and 69.8%, respectively. Histopathological changes and mast cell migration in treated animals with JR-12 or JR09-Bz were similar to treatment with the reference drugs dexamethasone and montelukast. JR-12 and JR09-Bz also reversed airway remodeling in animals on the bleomycin-induced fibrosis model compared to the control group. Furthermore, it was observed that N-arylhydrazone derivatives showed expectorant and mucolytic activities, increasing mucus secretion by 45.6% and 63.8% for JR-12 and JR09-Bz, respectively. CONCLUSION: Together, the results show that JR-12 and JR09-Bz showed promising activity against airway inflammation, as well as low toxicity.

The phytochemical constituents and protective effect of Fritillaria hupehensis on acute lung injury.

Acute lung injury (ALI), a severe respiratory disorder, frequently develops into acute respiratory distress syndrome (ARDS) without timely treatment and scores highly in terms of morbidity and mortality rates. Fritillaria hupehensis is a famous traditional Chinese medicine with antitussive, expectorant and anti-asthmatic effect. Here, the effects of F. hupehensis extracts on lipopolysaccharide (LPS)-induced ALI mice were evaluated for the first time. We showed ethyl acetate fraction (EAF) significantly reduced the leukocytes and neutrophils of bronchoalveolar lavage fluid (BALF) and the lung index as well as pro-inflammatory cytokines (TNF-α and IL-6) of lung homogenates but increasing the anti-inflammatory cytokines (IL-4 and IL-10). Additionally, the alleviation of EAF treatment on lung injury was verified through histopathological observations. Subsequent phytochemical investigation on bioactive fraction led to isolation of 17 compounds including two new, in which compounds 2, 5 and 6 exhibited better anti-inflammatory effect on LPS-induced 16 human airway epithelial (16HBE) cells model by inhibiting the production of CRP and PCT. Furthermore, compound 2 suppressed the LPS-induced upregulation of proteins containing p-p65, COX-2, Caspase-1 and IL-18. In summary, F. hupehensis alleviating LPS-induced ALI in mice may be associated with the anti-inflammatory activity of steroidal alkaloids by suppressing the NF-κB-regulated pro-inflammatory proteins.

Dornase alfa for cystic fibrosis.

BACKGROUND: Dornase alfa is currently used as a mucolytic to treat pulmonary disease (the major cause of morbidity and mortality) in cystic fibrosis. It reduces mucus viscosity in the lungs, promoting improved clearance of secretions. This is an update of a previously published review. OBJECTIVES: To determine whether the use of dornase alfa in cystic fibrosis is associated with improved mortality and morbidity compared to placebo or other medications that improve airway clearance, and to identify any adverse events associated with its use. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises references identified from comprehensive electronic database searches, handsearching relevant journals and abstracts from conferences. Date of the most recent search of the Group's Cystic Fibrosis Register: 12 October 2020. Clinicaltrials.gov and the International Clinical Trials Registry Platform were also searched to identify unpublished or ongoing trials. Date of most recent search: 08 February 2021. SELECTION CRITERIA: All randomised and quasi-randomised controlled trials comparing dornase alfa to placebo, standard therapy or other medications that improve airway clearance. DATA COLLECTION AND ANALYSIS: Authors independently assessed trials against the inclusion criteria; two authors carried out analysis of methodological quality and data extraction. GRADE was used to assess the level of evidence. MAIN RESULTS: The searches identified 74 trials, of which 19 (2565 participants) met our inclusion criteria. 15 trials compared dornase alfa to placebo or no dornase alfa (2447 participants); two compared daily dornase to hypertonic saline (32 participants); one compared daily dornase alfa to hypertonic saline and alternate day dornase alfa (48 participants); one compared dornase alfa to mannitol and the combination of both drugs (38 participants). Trial duration varied from six days to three years. Dornase alfa compared to placebo or no treatment Dornase alfa probably improved forced expiratory volume at one second (FEV1) at one month (four trials, 248 participants), three months (one trial, 320 participants; moderate-quality evidence), six months (one trial, 647 participants; high-quality evidence) and two years (one trial, 410 participants). Limited low-quality evidence showed treatment may make little or no difference  in quality of life. Dornase alfa probably reduced the number of pulmonary exacerbations in trials of up to two years (moderate-quality evidence). One trial that examined the cost of care, including the cost of dornase alfa, found that the cost savings from dornase alfa offset 18% to 38% of the medication costs. Dornase alfa: daily versus alternate day One cross-over trial (43 children) found little or no difference between treatment regimens for lung function, quality of life or pulmonary exacerbations (low-quality evidence). Dornase alfa compared to other medications that improve airway clearance Results for these comparisons were mixed. One trial (43 children) showed dornase alfa may lead to a greater improvement in FEV1 compared to hypertonic saline (low-quality evidence), and one trial (23 participants) reported little or no differences in lung function between dornase alfa and mannitol or dornase alfa and dornase alfa plus mannitol (low-quality evidence). One trial (23 participants) found dornase alfa may improve quality of life compared to dornase alfa plus mannitol (low-quality evidence); other comparisons found little or no difference in this outcome (low-quality evidence). No trials in any comparison reported any difference between groups in the number of pulmonary exacerbations (low-quality evidence). When all comparisons are assessed, dornase alfa did not cause significantly more adverse effects than other treatments, except voice alteration and rash. AUTHORS' CONCLUSIONS: There is evidence to show that, compared with placebo, therapy with dornase alfa may improve lung function in people with cystic fibrosis in trials lasting from one month to two years. There was a decrease in pulmonary exacerbations in trials of six months or longer, probably due to treatment. Voice alteration and rash appear to be the only adverse events reported with increased frequency in randomised controlled trials. There is not enough evidence to firmly conclude if dornase alfa is superior to other hyperosmolar agents in improving lung function.

Use of mucolytics in COPD: A Delphi consensus study.

BACKGROUND: International guidelines recommend mucolytic agents as add-on therapy in selected patients with COPD because they may reduce exacerbations and improve health status. As the evidence varies among mucolytic agents, we used the Delphi method to assess consensus amongst an international panel of COPD experts on mucolytics use in COPD. METHODS: 53 COPD experts from 12 countries were asked to complete an online questionnaire and rate their agreement with 15 statements using a 5-point scale. The mucolytic agents evaluated were carbocysteine, erdosteine and N-acetylcysteine (NAC). Data were collected anonymously and consensus presented using descriptive statistics. RESULTS: The 47 respondents reached consensus on the statements. They agreed that regular treatment with mucolytic agents effectively reduces the frequency of exacerbations, reduces the duration of mild-to-moderate exacerbations, and can increase the time to first exacerbation and symptom-free time in COPD patients. Consensus was consistently highest for erdosteine. The experts agreed that all three mucolytics display antioxidant and anti-inflammatory activity. Erdosteine and NAC were thought to improve the efficacy of some classes of antibacterial drugs. All three mucolytics were considered effective for the short-term treatment of symptoms of acute exacerbations when added to other drugs. The panel agreed that approved doses of mucolytic agents have favorable side-effect profiles and can be recommended for regular use in patients with a bronchitic phenotype. CONCLUSIONS: Consensus findings support the wider use of mucolytic agents as add-on therapy for COPD. However, the differences in pharmacological actions and clinical effectiveness must be considered when deciding which mucolytic to use.

Effect of Erdosteine on COPD Exacerbations in COPD Patients with Moderate Airflow Limitation.

Background: The RESTORE study, a multi-national randomized, placebo-controlled study, showed that erdosteine - a muco-active antioxidant that modulates bacterial adhesiveness - reduced the rate and duration of exacerbations in moderate and severe COPD with a history of exacerbations. How much benefit patients with less severe disease experience when taking this drug remains unclear. Methods: This post hoc analysis of the 254 RESTORE participants with spirometrically-defined moderate COPD (post-bronchodilator forced expiratory volume in 1 second [FEV1] 50‒79% predicted) examined exacerbation rate and duration, time to first exacerbation, and exacerbation-free time. Data were analyzed using descriptive statistics and comparisons between treatment groups used Wilcoxon rank-sum tests, Mann-Whitney U-tests, or log rank tests. Results: Patients with moderate COPD received erdosteine 300 mg twice daily (n=126) or placebo (n=128) added to usual COPD therapy for 12 months. During this time, there were 53 exacerbations in the erdosteine group and 74 in the placebo group, with 42.1% and 57.8% of patients, respectively, experiencing an exacerbation. There was a 47% reduction in the mean exacerbation rate with erdosteine compared to placebo (0.27 vs 0.51 exacerbations per-patient per-year, respectively, P=0.003), and a 58.3% reduction in the mild exacerbation rate (0.23 vs 0.53 mild exacerbations per-patient per-year, P=0.001). Mean duration of exacerbations was 26% shorter in erdosteine-treated patients (9.1 vs 12.3 days for placebo, P=0.022), with significant reductions in the duration of mild and moderate-to-severe exacerbations. Mean time to first exacerbation was prolonged by 7.7% (182 days for erdosteine vs 169 days for placebo, P<0.001) and the mean exacerbation-free time was increased by 51 days (279 days for erdosteine vs 228 days for placebo; P<0.001). Conclusion: These results indicate that adding erdosteine to usual COPD maintenance therapy reduces the number of mild, and duration of all, exacerbations in patients with moderate COPD and a history of exacerbations.

Efficacy and safety profile of mucolytic/antioxidant agents in chronic obstructive pulmonary disease: a comparative analysis across erdosteine, carbocysteine, and N-acetylcysteine.

BACKGROUND: To date there are no head-to-head studies comparing different mucolytic/antioxidant agents. Considering the inconsistent evidence resulting from the pivotal studies on mucolytic/antioxidant agents tested in chronic obstructive pulmonary disease (COPD), and the recent publication of Reducing Exacerbations and Symptoms by Treatment with ORal Erdosteine in COPD (RESTORE) study, we have performed a meta-analysis to compare the efficacy and safety of erdosteine 600 mg/day, carbocysteine 1500 mg/day, and N-acetylcysteine (NAC) 1200 mg/day in COPD. METHODS: A pairwise and network meta-analyses were performed to assess the efficacy of erdosteine, carbocysteine, and NAC on acute exacerbation of COPD (AECOPD), duration of AECOPD, and hospitalization. The frequency of adverse events (AEs) was also investigated. RESULTS: Data obtained from 2753 COPD patients were extracted from 7 RCTs published between 2004 and 2017. In the pairwise meta-analysis mucolytic/antioxidant agents significantly reduced the risk of AECOPD (RR 0.74 95%CI 0.68-0.80). The network meta-analysis provided the following rank of effectiveness: erdosteine>carbocysteine>NAC. Only erdosteine reduced the risk of experiencing at least one AECOPD (P < 0.01) and the risk of hospitalization due to AECOPD (P < 0.05). Erdosteine and NAC both significantly reduced the duration of AECOPD (P < 0.01). The AEs induced by erdosteine, carbocysteine, and NAC were mild in severity and generally well tolerated. The quality of evidence of this quantitative synthesis is moderate. CONCLUSIONS: The overall efficacy/safety profile of erdosteine is superior to that of both carbocysteine and NAC. Future head-to-head studies performed on the same COPD populations are needed to definitely confirm the results of this meta-analysis. TRIAL REGISTRATION: CRD42016053762 .

A pilot study of safety of sulfamethoxazole, trimethoprim and guaifenesin in pediatric and adult patients with acute bronchitis.

OBJECTIVE: This exploratory study assessed the safety of the combination of sulfamethoxazole, trimethoprim and guaifenesin (STG) in adult and pediatric patients with acute bronchitis according to local labelling in Peru. RESULTS: We enrolled 51 pediatric and 52 adult participants diagnosed with acute bronchitis and indication of STG. The mean ages were 7.6 years (SD ± 3.2 years) and 42.8 years (SD ± 16.1) and the proportion of female patients were 51% and 65%, respectively. The duration of treatment in pediatric patients was < 5 days in 2% of patients, 5 days in 13.7%, 6-7 days, in 82.4% and > 7 days in 2% while in adults patients it was < 5 days in 17%, 5 days in 69.2%; 6-7 days in 28.8% of patients. Adverse events (AEs) were registered in 9.6% and 19.2% of pediatric and adult patients, respectively. These AEs had definite relation of causality with the study drugs in 2 adults (20% of AEs) and possible causality with the study drugs in 4 pediatric (80% of AEs) and 2 adult cases (20% of AEs). Our results provide valuable data to develop trials of pharmacovigilance where different statistical parameters should be considered to calculate an adequate sample size in studies evaluating STG in pediatric or adult patients. Trial registration NCT02879981 and NCT02902640.

Intraluminal therapy for Helicobacter pylori infection.

BACKGROUND AND AIM: Several strategies have been proposed to increase the eradication rate of Helicobacter pylori. However, the widespread increasing resistance rates to current multiple-dose oral antibiotic therapies call for alternative therapeutic approaches. We aim to develop a novel intraluminal therapy for H. pylori infection (ILTHPI). METHODS: From April 2017 to December 2017, 100 H. pylori-infected treatment-naïve patients with upper abdominal pain or discomfort underwent endoscopic examinations and concomitant ILTHPI, which comprised the control of intragastric pH, the irrigation of gastric mucosal surface with a mucolytic agent, and the application of single-dose medicaments containing antibiotic powders. The safety profiles while conducting ILTHPI and adverse events after ILTHPI were evaluated. The success of eradication was assessed based on the result of the 13 C-urea breath test 6 weeks after ILTHPI. In addition, a patient with successful ILTHPI was reconfirmed by a negative H. pylori stool antigen test four to 6 months after ILTHPI to exclude short-term recurrence. RESULTS: All the 100 enrolled patients completed the ILTHPI with good safety profiles and mild adverse events (6%). Five patients dropped out, and 51 of 95 patients (53.7%) achieved successful eradication immediately after endoscopic examinations. All 51 patients revealed negative stool H. pylori antigen tests four to 6 months after successful ILTHPI. No short-term recurrence was observed. CONCLUSIONS: We have developed a novel therapeutic approach. With the ILTHPI, H. pylori can be eradicated immediately by administrating a single-dose regimen while conducting an endoscopic examination. CLINICAL TRIALS NUMBER: NCT03124420.

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.

Pharmacokinetics and safety of salbutamol/ambroxol fixed-dose combination granules in healthy Chinese subjects
.

OBJECTIVES: The aim of the study was to investigate the pharmacokinetics and tolerability of salbutamol/ambroxol fixed-dose combination granules following single and multiple dosing in healthy Chinese subjects. MATERIALS AND METHODS: This was a randomized, open-label, two-period, one-sequence study (n = 12). Each subject received a single oral dose in period 1 and multiple doses in period 2. Plasma concentrations of these two components were determined using a validated LC-MS/MS method. Adverse events (AEs) were documented throughout the study. Investigators evaluated AEs in terms of frequency, duration, intensity, seriousness, outcome, and relationship to study drugs. RESULTS: Following single dosing, Cmax values were 8.07 ± 1.31 ng/mL and 25.7 ± 6.5 ng/mL for salbutamol and ambroxol, respectively. The corresponding T1/2 values were 8.15 ± 3.13 hours and 9.31 ± 2.27 hours, respectively. Moreover, no statistical differences in the pharmacokinetics of salbutamol and ambroxol in subjects receiving single or multiple dosage were observed. Single- and multiple-dose oral administration of fixed-dose combination granules were safe and well tolerated in healthy Chinese subjects. Drug hypersensitivity syndrome did not occur during our study. CONCLUSION: The pharmacokinetics of salbutamol and ambroxol in the fixed-dose combination granules were not affected by dosing duration, and gender differences seemed to have no effect on the pharmacokinetics of salbutamol and ambroxol after a single dose and multiple doses of the medication.
.

Dornase alfa for cystic fibrosis.

BACKGROUND: Dornase alfa is currently used as a mucolytic to treat pulmonary disease (the major cause of morbidity and mortality) in cystic fibrosis. It reduces mucus viscosity in the lungs, promoting improved clearance of secretions. This is an update of a previously published review. OBJECTIVES: To determine whether the use of dornase alfa in cystic fibrosis is associated with improved mortality and morbidity compared to placebo or other medications that improve airway clearance, and to identify any adverse events associated with its use. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises references identified from comprehensive electronic database searches, handsearching relevant journals and abstracts from conferences. Date of the most recent search of the Group's Cystic Fibrosis Register: 23 April 2018.Clinicaltrials.gov and the International Clinical Trials Registry Platform were also searched to identify unpublished or ongoing trials. Date of most recent search: 07 June 2018. SELECTION CRITERIA: All randomised and quasi-randomised controlled trials comparing dornase alfa to placebo, standard therapy or other medications that improve airway clearance. DATA COLLECTION AND ANALYSIS: Authors independently assessed trials against the inclusion criteria; two authors carried out analysis of methodological quality and data extraction. GRADE was used to assess the level of evidence. MAIN RESULTS: The searches identified 69 trials, of which 19 (2565 participants) met our inclusion criteria. Fifteen trials compared dornase alfa to placebo or no dornase alfa (2447 participants); two compared daily dornase to hypertonic saline (32 participants); one compared daily dornase alfa to hypertonic saline and alternate day dornase alfa (48 participants); one compared dornase alfa to mannitol and the combination of both drugs (38 participants). Trial duration varied from six days to three years.Dornase alfa compared to placebo or no treatmentDornase alfa improved forced expiratory volume at one second at one month (four trials, 248 participants), three months (one trial, 320 participants; moderate-quality evidence), six months (one trial, 647 participants; high-quality evidence) and two years (one trial, 410 participants). Limited low-quality evidence showed no difference between groups for changes in quality of life. There was a decrease in pulmonary exacerbations with dornase alfa in trials of up to two years (moderate-quality evidence). One trial that examined the cost of care, including the cost of dornase alfa, found that the cost savings from dornase alfa offset 18% to 38% of the medication costs.Dornase alfa: daily versus alternate dayOne cross-over trial (43 children) found no differences between treatment regimens for lung function, quality of life or pulmonary exacerbations (low-quality evidence).Dornase alfa compared to other medications that improve airway clearanceResults for these comparisons were mixed. One trial (43 children) showed a greater improvement in forced expiratory volume at one second for dornase alfa compared to hypertonic saline (low-quality evidence), and one trial (23 participants) reported no difference in lung function between dornase alfa and mannitol or dornase alfa and dornase alfa plus mannitol (low-quality evidence). One trial (23 participants) found a difference in quality of life favouring dornase alfa when compared to dornase alfa plus mannitol (low-quality evidence); other comparisons found no difference in this outcome (low-quality evidence). No trials in any comparison reported any difference between groups in the number of pulmonary exacerbations (low-quality evidence).When all comparisons are assessed, dornase alfa did not cause significantly more adverse effects than other treatments, except voice alteration and rash. AUTHORS' CONCLUSIONS: There is evidence to show that, compared with placebo, therapy with dornase alfa improves lung function in people with cystic fibrosis in trials lasting from one month to two years. There was a decrease in pulmonary exacerbations in trials of six months or longer. Voice alteration and rash appear to be the only adverse events reported with increased frequency in randomised controlled trials. There is not enough evidence to firmly conclude if dornase alfa is superior to other hyperosmolar agents in improving lung function.