Zataria multiflora affects pulmonary function tests, respiratory symptoms, bronchodilator drugs use and hematological parameters in chronic obstructive pulmonary disease patients: A randomized doubled-blind clinical trial.

ETHNOPHARMACOLOGICAL RELEVANCE: Zataria multiflora is employed as an antitussive, anti-spasmodic, analgesic and etc. Agent in traditional medicine. The modern medical studies are also confirmed effects of this plant for treatment of respiratory problems via anti-inflammatory, anti-oxidant and immunomodulatory properties. AIM OF STUDY: We evaluated efficacy of Z. multiflora on tests of pulmonary function, respiratory symptoms, inhaled bronchodilator drugs use, and hematological factors in COPD patients. METHODS: Patients (n = 45) were randomly grouped in the following three groups: placebo group (P), groups received Z. multiflora extract 3 and 6 mg/kg/day (Z3 and Z6). FEV1 and MEF25-75, respiratory symptoms, inhaled bronchodilator drugs use and hematological factors were evaluated before and 1-2 months after treatment. RESULTS: Z. multiflora led to significant enhancement of FEV1 (p < 0.05 to p < 0.01). Respiratory symptoms were also considerably ameliorated following treatment with extracts for 1 and 2 months compared to baseline values (p < 0.05 to p < 0.001). In groups received extract, inhaled bronchodilator drugs use was remarkably declined at the end of study (both, p < 0.05). Reduction of total WBC was observed 1-2 months after treatment in treated groups with extract compared to baseline values (p < 0.05 to p < 0.001). Neutrophils were remarkably declined in Z3 and Z6 groups after 2-monthes compared to 1-month treatment (p < 0.05 to p < 0.01). CONCLUSION: The evidence show therapeutic effect of this herb on COPD patients which could be result from properties that help to decrease inflammation.

The association between MUC5AC and MUC5B genes expression and remodeling progression in severe neutrophilic asthma: A direct relationship.

BACKGROUND: MUC5 dysregulation is a hallmark of severe neutrophilic asthmatic patients. This study investigates the expression of MUC5AC and MUC5B at mRNA levels on asthma severity and airway wall thickness in severe neutrophilic asthmatic patients. METHOD: In this case-control clinical trial, twenty-five severe neutrophilic asthmatic patients and ten control subjects were enrolled. Subjects underwent ACT, pulmonary functions tests, and fractional exhaled nitric oxide (FENO). Also, induced sputum has been obtained to assess the expression of MUC5AC and MUC5B by the real-time PCR. In addition, the thickness of the airway wall was assessed by high-resolution computed tomography (HRCT), and bioinformatic analysis was implemented to approve the selection of the appropriate genes and for further investigations. RESULT: A significant difference was observed between the asthmatic and control in MUC5AC and MUC5B mRNA expression. Meanwhile, the expression of MUC5AC increased remarkably by asthma severity; also, it is associated with airway wall thickness (WT) (both P-value <0.05). The expression of MUC5B in asthmatic patients was lower than in control. There is no significant correlation between MUC5B mRNA level and WT and asthma severity. Notably, MUC5AC transcription level was correlated to sputum neutrophil percentage, while MUC5B transcription level had a positive correlation with sputum macrophages and a negative one with sputum neutrophils. CONCLUSION: In severe neutrophilic asthma, airway wall thickness increases with MUC5AC mRNA overexpression, which is probably related to asthma severity and the formation of mucus plugs. However, the expression of MUC5B was decreased, resulting in poor mucociliary clearance in the airways. TRIAL REGISTRATION: IR.IAU.MSHD.REC.1400.124.

Itraconazole Improved Bronchial Wall Thickness in Severe Persistent Asthma: A Double-blind Placebo-controlled Randomized Clinical Trial.

The purpose of this study was to evaluate the effect of 8 months of treatment with itraconazole on airway wall thickness in patients with severe persistent asthma. It was a double-blind, randomized, placebo-controlled clinical trial (IRCT20091111002695N9). Seventy-five subjects with severe persistent asthma received itraconazole (100 mg), prednisolone (5 mg), or placebo twice a day for eight months in three treatment groups (n=25 in each group). The primary objective was to improve the right upper lobe apical segmental bronchus (RB1) wall thickness percentage measured by high-resolution computed tomography scan of the lungs. Other morphometric measurements of RB1, asthma control test (ACT) score, presence of wheezing, dyspnea severity, rate of asthma exacerbation, fractional exhaled nitric oxide (FeNO), and expiratory volume in 1 second (FEV1) were set as the secondary outcomes. Wall thickness percentage reduced significantly from 46% to 43.7% from pre- to post-treatment in the itraconazole-treated subjects. Similarly, lumen area and radius increased significantly in both the prednisolone and itraconazole groups. Itraconazole led to a significant improvement in wheezing, dyspnea severity, FEV1, ACT score, and FeNO. Although prednisolone was also effective in improving pulmonary function tests and ACT scores, it was associated with significantly more side effects than itraconazole. Long-term treatment with itraconazole resulted in a significant reduction in bronchial wall thickness and improvements in clinical findings and pulmonary function tests. Thus, itraconazole could be a helpful add-on treatment option for severe persistent asthma patients to achieve better disease control.

Comparison of the effects of itraconazole and prednisolone on fibroblast growth factor-2 gene expression and clinical manifestations in patients with persistent severe asthma.

Background and Purpose: Considering the possible role of fungal sensitization in the treatment of resistant asthma, which may lead to the remodeling of bronchial structure, we theorized that itraconazole could result in better control of asthma. In this regard, this study aimed to compare the effects of itraconazole and prednisolone (routinely prescribed) on clinical, structural, and biomarker findings of the remodeling of asthma. Materials and Methods: This double-blind controlled randomized clinical trial was performed on 70 adult patients suffering from severe persistent asthma. The intervention group received 200 mg of itraconazole per day, and the control group received 10 mg of prednisolone per day, for 32 weeks, in addition to the classic treatment of asthma. The subjects were randomly divided into two groups, and assigned by sealed envelope. Blinding was performed by repacking the drug in a similar container. Primary outcomes were asthma control test score, fibroblast growth factor 2, and wall area percentage on RB1 bronchus measured by computed tomography. The outcomes were compared in subjects classified as allergic, eosinophilic, T2 low asthma, and four types of inflammatory cell classification in sputum. Results: Seventy subjects finished the 32-week trial (35 subjects in each group). Baseline data did not show significant differences between groups. A comparison of asthma variants showed significantly more severe cough and dyspnea in the allergic variant and higher spirometry results in T2-low asthma. Sputum cytology revealed a mixed pattern as the most frequent type (47%). After the trial, two groups improved in many parameters; however, FGF-2 improved more significantly by itraconazole (4.66±16.92 decreased to 1.14±2.98), and FEV1/FVC was significantly higher in the itraconazole group, compared to the control group. These results did not change in terms of asthma variants and sputum classification. Conclusion: Itraconazole was superior to prednisolone in the treatment of many clinical and spirometry aspects in severe persistent asthma.

Effective Treatment of Chronic Cough with Tinidazole as the Newest Antiprotozoa against Lophomonas blattarum.

Background: Chronic cough is a common problem in the setting of family physicians. Recently, Lophomonas blattarum was considered a cause of respiratory symptoms in children and adults. Objective: This study is aimed at determining the effect of antiprotozoal treatment of Lophomonas in patients with a chronic cough in Mashhad during 2020-2021. Materials and Methods: This study was a randomized clinical trial. In this study, 60 patients with chronic cough and unremarkable imaging findings, who were unresponsive to three steps of standard treatment, were randomly assigned to the treatment, with 2 weeks of tinidazole and placebo. The tinidazole and placebo were prepared in a completely identical shape, and a random assignment was performed by a third party. The primary outcome was a complete resolution of cough. A follow-up of treatment was performed. Data were analyzed using the SPSS software version 25. Results: The basic demographic results showed no significant differences of sex and age between two groups. The results of this study showed a complete resolution of all respiratory symptoms in 40% (12), a complete improvement of cough in 40% (12), and a complete resolution of dyspnea in 50% (10) of the tinidazole group. The remaining showed significant improvement in the severity of cough and dyspnea. Postnasal drip, sputum, body temperature, and airway hyperresponsiveness were improved significantly. After tinidazole treatment, laboratory assessment of bronchial lavage and sputum revealed that 86 percent of smears were converted to negative. Conclusion: Tinidazole effectively resolved the chronic cough and most of the respiratory symptoms. Lophomonas blattarum is a potential mechanism for chronic cough.

Effect of Propolis on moderate persistent asthma: A phase two randomized, double blind, controlled clinical trial.

OBJECTIVE: The aims of this study was to determine the effect of Propolis (resinous mixture that honey bees produce by mixing saliva and beeswax) on clinical and physiological findings of moderate persistent asthma. MATERIALS AND METHODS: Fifty-two subjects aged 44.6±18.5 years old with moderate asthma and Forced expiratory volume in 1 second (FEV1) 60-79% of predicted, were enrolled in this clinical trial. We randomly allocated subjects to receive either propolis (75 mg three times a day) or a matched placebo for one month. Primary outcome was Asthma control test (ACT) score and secondary outcomes included dyspnea, spirometry, fractional exhaled nitric oxide (FENO) and sputum cytology including inflammatory cell. Sputum induction was done by hypertonic saline and cytology slides were stained by Papanicolaou stain. RESULTS: Clinical findings significantly improved after the treatment. ACT scores significantly increased by using propolis (12.8±5.5 before and 18.1±4.99 after the trial), which was significantly higher than the placebo group (14.4±6.6 after the trial). The most significant physiological improvements were significant increases in FEV1, FV1/Forced vital capacity and expiratory flows. FENO showed significant decreases in the propolis group but increases in the placebo group. Cytological examination of sputum showed that the pattern of inflammation was eosinophilic in 44% subjects with an average eosinophil of 7.2±1.01%. Eosinophilia significantly decreased (p<0.05) by using propolis (7.2±1.01 and 4.3±3.1%, before and after treatment, respectively), but it significantly increased (p<0.04) in the placebo group (5.5±2.8, and 11.1±6.6%, before and after treatment, respectively). CONCLUSION: Propolis improved the clinical and physiological findings of moderate persistent asthma, and it was able to suppress eosinophilic inflammation.

Long-term effect of antifungal therapy for the treatment of severe resistant asthma: an active comparator clinical trial.

BACKGROUND AND PURPOSE: Itraconazole therapy has been reported to control asthma in severe therapy-resistant asthma with fungal sensitization. The aim of this study was to investigate the impact of anti-fungal therapy on the treatment of severe asthma, irrespective of sensitization. MATERIALS AND METHODS: This active comparator clinical trial was performed on 110 therapy-resistant asthmatic patients who were randomly assigned into two groups of case and control. The patients in the case group were administered 200 mg itraconazole twice a day and the control group received 10 mg prednisolone after breakfast for 4 months. The asthma control test (ACT) which was used as a marker for the global evaluation of treatment effectiveness (GETE) was applied as the primary endpoint parameter. Cough, dyspnea, and sleep disturbance were measured on a scale of 1-4, with 1 representing no symptom and 4 indicating severe exhausting disturbance. RESULTS: Based on the obtained results, 71% of the itraconazole group demonstrated a marked improvement in the GETE score after a four-month treatment. Itraconazole was able to suppress clinical symptoms, including cough, dyspnea, and night symptoms, and their physical exam was indicative of normalization in 60% of the patients. On the other hand, the patients in the parallel group "prednisolone" were only able to control dyspnea. The ACT score represented a notable improvement with itraconazole (mean: 14 before the trial and >20 after the trial) and spirometry parameters underwent a considerable change from obstructive pattern to normal. Furthermore, adverse effects were only detected in 6% of itraconazole users. CONCLUSION: The results of this clinical trial indicted the effectiveness of antifungal therapy for the control of the clinical condition of a subgroup of patients with severe steroid-refractory asthma.

Effects of Rosmarinus officinalis and Platanus orientalis extracts on asthmatic subjects resistant to routine treatments.

OBJECTIVE: The present study aimed to determine the effects of Rosmarinus officinalis (R. officinalis) and Platanus orientalis (P. orientalis) extracts on asthma. MATERIALS AND METHODS: We conducted a randomized, double-blind, active-comparator study to evaluate the effect of P. orientalis and R. officinalis extracts on asthmatic patients resistant to routine treatment. The subjects were randomly divided into three groups receiving P. orientalis and R. officinalis extracts alone or in combination. The primary endpoints were clinical findings, spirometry, exhaled nitric oxide (FENO) and Asthma Control Test (ACT) assessed over the one-month treatment period. RESULTS: ACT score showed significant improvement after treatment with R. officinalis (p<0.05) but not with P. orientalis. Clinical evaluations showed that cough, sputum production and wheezing were significantly improved in R. officinalis group (p<0.05 to p<0.001) while in P. orientalis group only improvement of cough and chest tightness were shown. Spirometry results showed significant improving in FEV1/VC values for subjects treated with P. orientalis and those who received the combination of extracts as well as significant decrease in FEF25-75 value only for P. orientalis group (p<0.05 for all cases). FENO was decreased in both groups but the results were statistically significant only for R. officinalis group (p<0.05). Abdominal pain and skin rash were the most frequent side effects of the treatments which led to discontinuation of the intervention. CONCLUSION: R. officinalis extract showed promising results in treatment of resistant asthma. Further studies to find the most effective components of these herbal medicines are recommended.

Effect of Salmeterol-Fluticasone Combination and Tiotropium on Clinical and Physiological Improvement of Bronchial Anthracofibrosis: a Double Blind Randomized, Cross Over, Placebo Controlled, Clinical Trial.

BACKGROUND: Bronchial anthracosis is the black discoloration of bronchial mucosa that exhibits similar manifestations to Chronic Obstructive Pulmonary Disease ( COPD). The etiology of this obstructive lung disease has not been elucidated and standard therapy for this disease has not been introduced in the literature. The objective of this study is to determine the efficacy of the salmeterol-fluticasone inhaler and tiotropium as two safe treatments of obstructive lung disease for the treatment of symptomatic subjects of anthracofibrosis of the lung. MATERIALS AND METHODS: Twenty anthracofibrosis subjects who suffered from dyspnea were enrolled in this three-phase, cross over, placebo-controlled clinical trial. The primary outcome variable was quality of life (evaluated with the CAT questionnaire). Clinical findings and spirometry were the secondary outcome variables. Both of these drugs were delivered by an inhaler and were made identically by the reference manufacturer. Salmeterol-fluticasone was prescribed with a spacer and tiotropium by its special device, and the method of utilization was taught to the patients. RESULTS: Twenty anthracofibrosis subjects were enrolled in this three-phase, five-month course of treatment with either salmeterol-fluticasone or tiotropium inhalers. The response to therapy was not good; neither for salmeterol-fluticasone nor for tiotropium in the short course of the treatment. However, the overall results of 5 months of therapy with both of the drugs have shown improvement in 57% of the subjects. The most prominent results were found in the CAT score [25.1±5.54 before the trial, which decreased to 19.2±5.14 (Z score=2.7, P=0.007)] and clinical findings especially sputum, chest pain, and wheezing (81, 94 and 92% before the trial and 50, 56, 54% after the trial, respectively). Neither clinical findings nor spirometry was able to predict a good response to salmeterol-fluticasone or tiotropium. CONCLUSION: The combination of salmeterol-fluticasone and tiotropium inhaler was able to improve the clinical findings of symptomatic anthracofibrosis patients.