[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.

A combination of Tropaeolum majus herb and Armoracia rusticana root for the treatment of acute bronchitis.

BACKGROUND: Tropaeolum majus herb (nasturtium) and Armoracia rusticana root (horseradish) produce three different isothiocyanates as secondary metabolites, which exert antibacterial, anti-inflammatory, and immune-modulatory functions in humans. PURPOSE: Combined in the medicinal product ANGOCIN® Anti-Infekt N, the two natural components demonstrated promising effects against acute bronchitis. STUDY DESIGN: A randomized, two-armed, placebo-controlled, double-blind, phase IV study revealed the healing fostering effect of the two herbal plant components METHODS: This study included 384 patients, with 195 in the treatment and 189 in the placebo group. The 'bronchitis severity score' (BSS) was utilized as primary endpoint. This score sums the ratings for five significant bronchitis symptoms, which are established at the patient's visits to the clinic. RESULTS: Compared to placebo intake, the group of patients treated with the phytomedicine showed statistically significant accelerated healing of bronchitis symptoms after three days of treatment, with reductions in coughing, mucous production, and chest pain. This beneficial effect persisted for the entire duration of treatment until day ten. CONCLUSION: In conclusion, a combination of Tropaeolum majus herb and Armoracia rusticana root promotes an elevated improvement of bronchitis symptomatology.

Prenatal exposure to synthetic phenols and phthalates and child respiratory health from 2 to 36 months of life.

Exposure to phthalates and synthetic phenols is ubiquitous. Some of them are suspected to impact child respiratory health, although evidence still remains insufficient. This study investigated the associations between prenatal exposure to phthalates and phenols, individually and as a mixture, and child respiratory health assessed by objective lung function measures since 2 months of age. Among 479 mother-child pairs from the SEPAGES cohort, 12 phenols, 13 phthalate and 2 non-phthalate plasticizer metabolites were measured in 2 pools including each 21 urine samples collected at the 2nd and 3rd pregnancy trimesters. Lung function was measured at 2 months using tidal breathing flow-volume loops and nitrogen multiple-breath washout, and at 3 years using oscillometry. Asthma, wheezing, bronchitis and bronchiolitis were assessed by repeated questionnaires. A cluster-based analysis was applied to identify exposure patterns to phenols and phthalates. Adjusted associations between clusters as well as each individual exposure biomarker and child respiratory health were estimated by regression models. We identified four prenatal exposure patterns: 1) low concentrations of all biomarkers (reference, n = 106), 2) low phenols-moderate phthalates (n = 162), 3) high concentrations of all biomarkers except bisphenol S (n = 109), 4) high parabens-moderate other phenols-low phthalates (n = 102). At 2 months, cluster 2 infants had lower functional residual capacity and tidal volume and higher ratio of time to peak tidal expiratory flow to expiratory time (tPTEF/tE) and cluster 3 had lower lung clearance index and higher tPTEF/tE. Clusters were not associated with respiratory health at 3 years but in the single-pollutant models, parabens were associated with increased area of the reactance curve, bronchitis (methyl, ethyl parabens) and bronchiolitis (propyl paraben). Our results suggested that prenatal exposure to mixtures of phthalates reduced lung volume in early life. Single exposure analyses suggested associations of parabens with impaired lung function and increased risk of respiratory diseases.

Ivy leaves extract EA 575 in the treatment of cough during acute respiratory tract infections: meta-analysis of double-blind, randomized, placebo-controlled trials.

Ivy leaves extracts have been used successfully to treat acute cough, and data from well-controlled trials is accumulating. We present a meta-analysis of two double-blind, randomized, placebo-controlled trials. Patients with acute respiratory tract infection (ARTI) received ivy leaves dry extract EA 575 (n = 228) or placebo (n = 162) for 7 days, followed by a 7-day period without treatment. The main efficacy outcome was the Bronchitis Severity Score (BSS). Individual patient data meta-analyses were performed using mixed models for repeated measures, analysis of covariance and logistic ordinal regression. Significant BSS differences between EA 575 and placebo occurred already after 2 days and increased until treatment end, with BSS reductions of 8.6 ± 0.2 and 6.2 ± 0.2 (marginal means ± SEM; p < 0.001). The score reduction for placebo after 7 days was comparable to that for EA 575 after 4 days. In the EA 575 group, the proportion of cough-free patients was 18.1% at treatment end and 56.2% at end of follow-up, compared to 9.3% and 25.6% for placebo, respectively. Adverse event rates for EA 575 and placebo were comparable. EA 575 reduces effectively the intensity of acute cough associated with ARTIs and leads to a significant acceleration of recovery. No safety signals were observed.

The efficacy and safety of DW1601 in patients with acute bronchitis: a multi-center, randomized, double-blind, phase III clinical trial.

BACKGROUND/AIMS: DW1601, an oral fixed dose combination syrup composed of DW16011 and Pelargonium sidoides, was developed to enhance the symptom relief effect in patients with acute bronchitis. We evaluated the efficacy and safety of DW1601 compared to DW16011 or P. sidoides for treatment of acute bronchitis using a randomized, double-blind, placebocontrolled, multi-centre trial design. METHODS: A total of 204 patients with acute bronchitis was randomized 1:1:1 to receive DW1601 (n = 67), DW16011 (n = 70), or P. sidoides (n = 64) for 7 days. The primary outcome was efficacy of DW1601 compared to DW16011 or P. sidoides in reducing the total bronchitis severity score (BSS) at day 4 of treatment. Secondary endpoints were changes in total and symptomspecific BSS, response rate and patient satisfaction rate. Safety analysis was assessed at day 7. RESULTS: At 4 days after medication, decrease of total BSS from baseline was significantly greater in the DW1601 group than in the DW16011 group (-3.51 ± 0.18 vs. -2.65 ± 0.18, p = 0.001) or P. sidoides group (-3.56 ± 0.18 vs. -2.64 ± 0.19, p < 0.001). In addition, the BSS total score at day 7 and the BSS cough and sputum component scores at days 4 and 7 were significantly more improved with DW1601 treatment compared with the DW16011 group or P. sidoides group. Participants treated with DW1601 showed higher rates of response and satisfaction than control groups (response rate, DW1601, 100% vs. DW16011, 85.7% vs. P. sidoides, 85.9%; satisfaction rate, DW1601, 92.6% vs. DW16011, 82.9% vs. P. sidoides, 81.2%). Significant adverse events were not observed in the DW1601 group. CONCLUSION: DW1601 is superior to DW16011 or P. sidoides in improving symptoms of acute bronchitis.

Pricing air pollution: evidence from short-term exposure to air pollution on hospitalization of acute bronchitis and chronic obstructive pulmonary disease in southwestern China.

Existing evidence suggests that ambient air pollution has serious adverse effects on respiratory diseases, yet there is little direct evidence from China regarding corresponding economic losses. Here we quantified air pollution-related acute health effects and related economic losses of the most common two respiratory diseases in southwestern China, acute bronchitis and chronic obstructive pulmonary disease (COPD). We applied a distributed lag non-linear model to analyse the relationship between ambient air pollutants and hospital admissions of acute bronchitis and COPD, then applied the cost of illness method to explore the attributing economic burden. During the study period, 528 334 and 99 419 hospital admissions of acute bronchitis and COPD, respectively, were recorded. As a result, during the study period the total hospitalization economic losses attributable to air pollution were 486.40 and 254.74 million yuan for acute bronchitis and COPD, respectively, accounting for 0.015% of local gross domestic product. Our research provides intuitive evidence on the health and economic impacts of short-term exposure to air pollution, which is a key basis for the formulation of environmental policies.

Air pollution and pediatric respiratory hospital admissions in Bursa, Turkey: A time series study.

We aimed to investigate the relation between air pollution and the number of daily hospitalizations due to pneumonia, asthma, bronchitis in children aged 0-18 in Bursa city of Turkey, between the years 2013-2018. The daily values of air pollutants (PM10, SO2, NO2, NOx, CO, and O3) from 2013 until 2018, were obtained. Adjusted Quasi-Poisson regression models including distributed lags, controlled for climate variables were used for data analysis. Increases in SO2, ozone, PMs, and nitrogen oxides were associated with pneumonia hospitalizations, increases in SO2 NOx and PMs were associated with asthma hospitalizations, and increases in SO2 and ozone were associated with bronchitis hospitalizations. Male hospitalization was related with SO2, ozone, and NOx; while female hospitalization was only related with SO2. This study showed that short-term exposure to air pollution is associated with an increased risk of pneumonia, asthma, and bronchitis hospitalization among children in Bursa.

An initial assessment of the involvement of transglutaminase2 in eosinophilic bronchitis using a disease model developed in C57BL/6 mice.

The detailed pathogenesis of eosinophilic bronchitis (EB) remains unclear. Transglutaminase 2 (TG2) has been implicated in many respiratory diseases including asthma. Herein, we aim to assess preliminarily the relationship of TG2 with EB in the context of the development of an appropriate EB model through ovalbumin (OVA) sensitization and challenge in the C57BL/6 mouse strain. Our data lead us to propose a 50 µg dose of OVA challenge as appropriate to establish an EB model in C57BL/6 mice, whereas a challenge with a 400 µg dose of OVA significantly induced asthma. Compared to controls, TG2 is up-regulated in the airway epithelium of EB mice and EB patients. When TG2 activity was inhibited by cystamine treatment, there were no effects on airway responsiveness; in contrast, the lung pathology score and eosinophil counts in bronchoalveolar lavage fluid were significantly increased whereas the cough frequency was significantly decreased. The expression levels of interleukin (IL)-4, IL-13, IL-6, mast cell protease7 and the transient receptor potential (TRP) ankyrin 1 (TRPA1), TRP vanilloid 1 (TRPV1) were significantly decreased. These data open the possibility of an involvement of TG2 in mediating the increased cough frequency in EB through the regulation of TRPA1 and TRPV1 expression. The establishment of an EB model in C57BL/6 mice opens the way for a genetic investigation of the involvement of TG2 and other molecules in this disease using KO mice, which are often generated in the C57BL/6 genetic background.

Long-Term Safety and Efficacy of Anifrolumab in Adults With Systemic Lupus Erythematosus: Results of a Phase II Open-Label Extension Study.

OBJECTIVE: To investigate long-term safety and tolerability of anifrolumab, a human monoclonal antibody to the type I interferon (IFN) receptor subunit 1, in patients with moderate-to-severe systemic lupus erythematosus (SLE). METHODS: This 3-year, multinational, open-label extension study included adult patients who completed treatment (48 weeks of anifrolumab or placebo; 12-week follow-up) in the MUSE phase IIb randomized controlled trial (RCT). Patients initially received 1,000 mg of anifrolumab intravenously every 4 weeks, which was reduced to 300 mg every 4 weeks based on the benefit/risk profile established in the MUSE trial. Adverse events (AEs) were assessed monthly. Exploratory end points included the SLE Disease Activity Index 2000 (SLEDAI-2K), Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI), pharmacodynamics, and health-related quality of life (HRQoL). RESULTS: Of the 246 patients who completed the RCT, 218 (88.6%) enrolled in the open-label extension study, of which 139 (63.8%) completed 3 years of treatment. Approximately 69.7% of patients reported ≥1 AE during the first year of open-label extension treatment. Frequency and patterns of serious AEs and AEs of special interest over 3 years were consistent with those reported for 1 year of treatment in the RCT. Few patients (6.9%) discontinued treatment due to AEs. No new safety signals were identified. Improvement in the SLEDAI-2K was sustained over 3 years. SDI and Short Form 36 health survey scores remained stable. Neutralization of type I IFN gene signatures was maintained in the IFN-high population, and C3, C4, and anti-double-stranded DNA showed trends toward sustained improvement. CONCLUSION: Long-term anifrolumab treatment demonstrates an acceptable safety profile with sustained improvement in SLE disease activity, HRQoL, and serologic measures.

E-Cigarettes and Other Electronic Nicotine Delivery Systems (ENDS).

Electronic nicotine delivery systems and vaping devices are now the most commonly used forms of tobacco consumed by youth and young adults. A variety of chemicals and toxicants released during inhalation have harmful systemic effects and effects on the lung. The known and potential health consequences are particularly alarming. There is concern that use of these devices will create a new generation of life-long smokers with nicotine and polysubstance addiction. Beyond the concerning chronic health effects of regular use, there is a recent epidemic of severe, acute lung disease termed e-cigarette, or vaping product use-associated lung injury, (EVALI), associated with high morbidity and mortality. These issues demand immediate public health attention. Healthcare providers play key roles in limiting the exposure of youth and young adults to these products by providing evidence-based counseling to patients and families, and by advocating for regulations to protect against childhood initiation and continuation of use.

Effect of NOx and NO2 Concentration Increase in Ambient Air to Daily Bronchitis and Asthma Exacerbation, Silesian Voivodeship in Poland.

There is a discussion in Europe about the dominant role of air pollution for health effects, most researchers claim that the particulate matter is responsible for inflammatory processes in the respiratory system, while others underline the role of nitrogen dioxide. The aim of the study was to assess the risk related to NOx, NO2 and PM2.5 concentration increase and daily outpatient visits or hospitalization due to bronchitis and asthma exacerbation in the entire population of Silesian Voivodeship, Poland. To assess the relationship between daily pollutants concentrations and the number of outpatient visits or hospitalizations due to bronchitis and asthma (available in the regional registry), the multivariable log-linear Poisson regression model was used. Results were presented by relative risk (RR) of health outcomes related to the increase in pollutant concentration by unit (interquartile range). Obtained results confirmed a statistically significant association between outpatient visits and hospitalizations due to bronchitis and asthma exacerbation and daily nitrogen oxides concentrations in Silesian voivodeship, Poland. The strongest relationship was observed in the case of NO2 and outpatient visits due to bronchitis, e.g., RR = 1.434 (1.308-1.571) for exposure expressed by the 50-day moving average concentration. In the case of hospitalizations, the health effect was lagged a few days in relation to the increase in exposure.

The Effect of Flavored E-cigarettes on Murine Allergic Airways Disease.

Flavored e-cigarettes are preferred by the majority of users yet their potential toxicity is unknown. Therefore our aim was to determine the effect of selected flavored e-cigarettes, with or without nicotine, on allergic airways disease in mice. Balb/c mice were challenged with PBS or house dust mite (HDM) (Days 0, 7, 14-18) and exposed to room air or e-cigarette aerosol for 30 min twice daily, 6 days/week from Days 0-18 (n = 8-12/group). Mice were exposed to Room Air, vehicle control (50%VG/%50PG), Black Licorice, Kola, Banana Pudding or Cinnacide without or with 12 mg/mL nicotine. Mice were assessed at 72 hours after the final HDM challenge. Compared to mice challenged with HDM and exposed to Room Air, nicotine-free Cinnacide reduced airway inflammation (p = 0.045) and increased peripheral airway hyperresponsiveness (p = 0.02), nicotine-free Banana Pudding increased soluble lung collagen (p = 0.049), with a trend towards increased airway inflammation with nicotine-free Black Licorice exposure (p = 0.089). In contrast, all e-cigarettes containing nicotine suppressed airway inflammation (p < 0.001 for all) but did not alter airway hyperresponsiveness or airway remodeling. Flavored e-cigarettes without nicotine had significant but heterogeneous effects on features of allergic airways disease. This suggests that some flavored e-cigarettes may alter asthma pathophysiology even when used without nicotine.

Associations of black carbon with lung function and airway inflammation in schoolchildren.

BACKGROUND: Few studies have investigated the 24-hour respiratory health effects of personal black carbon (BC) and ultrafine particles (UFP) exposure in schoolchildren. The objective of this study was to investigate these associations with the lung function in children 10-years old with and without persistent respiratory symptoms. METHODS: We conducted a cross-sectional study in 305 children (147 and 158 with and without persistent respiratory symptoms, respectively) from three European birth-cohorts: PARIS (France) and INMA Sabadell and Valencia (Spain). Personal 24-hour measurements of exposure concentrations to BC and UFP were performed by portable devices, before lung function testing. Forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and the fraction of exhaled nitric oxide (FeNO) were determined. RESULTS: There was no association of UFP with lung function parameters or FeNO whereas the increase in 24-hour BC exposure concentrations was related to a statistically significant decrease in lung function parameters only among children with persistent respiratory symptoms [-96.8 mL (95% Confidence Interval CI: -184.4 to -9.1 mL) in FVC, and -107.2 mL (95% CI: -177.5 to -36.9 mL) in FEV1 for an inter-quartile range of 1160 ng/m3 exposure increase]. A significant positive association between BC and FeNO was observed only in children with persistent respiratory symptoms with current wheezing and/or medication to improve breathing [FeNO increases with +6.9 ppb (95% CI: 0.7 to 13.1 ppb) with an inter-quartile range BC exposure increase]. CONCLUSION: Children suffering from persistent respiratory symptoms appear to be more vulnerable to BC exposure.

Ozone-primed neutrophils promote early steps of tumour cell metastasis to lungs by enhancing their NET production.

BACKGROUND: Air pollution, including particulates and gazes such as ozone (O3), is detrimental for patient's health and has repeatedly been correlated to increased morbidity and mortality in industrialised countries. Although studies have described a link between ambient particulate matter and increased lung cancer morbidity, no direct relation has yet been established between O3 exposure and metastatic dissemination to lungs. OBJECTIVES: To outline the mechanisms through which pulmonary O3 exposure modulates metastasis kinetics in an experimental mouse model of O3 exposure. METHODS: Metastatic responses to pulmonary O3 exposure were assessed using a reliable experimental mouse model of concomitant pulmonary O3 exposure and tumour cell injection. Roles of neutrophils in O3-induced lung metastasis were highlighted using blocking anti-Ly6G antibodies; moreover, the implication of neutrophil extracellular traps (NETs) in metastatic processes was evaluated using MRP8cre-Pad4lox/lox mice or by treating mice with DNase I. RESULTS: Pulmonary O3 exposure strongly facilitates the establishment of lung metastasis by (1) Inducing a pulmonary injury and neutrophilic inflammation, (2) Influencing very early steps of metastasis, (3) Priming neutrophils' phenotype to release NETs that favour tumour cell colonisation in lungs. The ability of O3-primed neutrophils to enhance lung colonisation by tumour cells was proven after their adoptive transfer in Balb/c mice unexposed to O3. CONCLUSIONS: Pulmonary neutrophils induced by O3 promote metastatic dissemination to lungs by producing NETs. These findings open new perspectives to improve treatment and prevention strategies in patients affected by metastatic diseases.

Hydrogen sulfide donor NaHS causes bronchitis with enhanced respiratory secretion in rats.

Inhalation of toxic gases is dangerous to humans; experiments using toxic gases themselves are also hazardous to researchers. Gas-releasing molecules are widely used as alternatives to toxic gases, but their impacts on the whole body remain to be examined. To investigate responses during hydrogen sulfide (H2S) poisoning, rats (Sprague-Dawley, male, 8-week-old) were intraperitoneally (i.p.) administered H2S donor, NaHS, and sacrificed 24 hr after the administration. The main histopathological finding commonly observed in NaHS-administered rat heart, liver, brain, and lung was congestion. In addition, inflammation and accumulation of mucopolysaccharides were observed in bronchioles of the lung. Immunoblot analysis indicated increasing trend of NF-κB activation, and real-time PCR analysis showed increasing tendency of TNFα and IL-1ß, as well as MUC1 and 5B, in NaHS-administered rat lung. Immunohistochemistry by use of anti-MUC1 and 5B antibodies confirmed enhanced mucosal secretion from bronchial epithelium. Moreover, administration of TNFα or IL-1ß to A549 lung epithelial cells resulted with enhanced expressions of MUC1 and 5B. This report shows bronchitis and respiratory mucosal secretion in animal model of H2S intoxication, which is created by i.p. administration of a H2S donor, through NF-κB-TNFα/IL-1ß-ΜUC1/5B pathway.

Safety of Oral Propranolol for Infantile Hemangioma.

OBJECTIVES: The safety of oral propranolol for infantile hemangioma has not yet been studied at population level since the pediatric use marketing authorization was obtained in Europe. METHODS: A survey of a nationwide, claim-based observational cohort of children <3 years old, with at least 1 delivery of oral propranolol between July 2014 and June 2016, was performed by using the database of the French National Health Insurance system. Standardized morbidity ratios (SMRs) were calculated by using, from the same database, a representative random sample of nonexposed subjects. The main outcomes were hospitalizations for cardiovascular (conduction disorders, bradycardia, and hypotension), respiratory (bronchial hyperactivity and bronchospasm), or metabolic events (hypoglycemia and hyperkalaemia), identified through the hospitalization diagnostic codes of the International Classification of Diseases, 10th Revision. The main analysis was conducted separately on "healthy" children (N = 1484), that is, free from of any prespecified underlying disease and on children with 1 of these underlying diseases (N = 269). RESULTS: In all, 1753 patients <3 years of age had at least 2 deliveries of oral propranolol. In the healthy population, we observed 2 cardiovascular events (SMR = 2.8 [0-6.7]), 51 respiratory events (SMR = 1.7 [1.2-2.1]), and 3 metabolic events (SMR = 5.1 [0-10.9]). In the population with an underlying disease (mainly congenital heart disease), we observed 11 cardiovascular events leading to an SMR of 6.0 (2.5-9.6). SMRs were not significantly raised for respiratory or metabolic events in this "nonhealthy" population. CONCLUSIONS: In this study on a large continuous nationwide claims database, we confirm the safety profile of oral propranolol in healthy children to be good.

Exposure to traffic-related air pollution and acute bronchitis in children: season and age as modifiers.

BACKGROUND: Acute bronchitis (AB) is one of the principal causes of childhood morbidity. Increasing number of studies has shown that air pollution is an important environmental contributor of respiratory disease. However, evidence so far is scarce regarding the effects of air pollution on childhood AB, and it also remains unclear how the risk of AB will change by season and age. METHODS: Data on hospital visits for AB in children, air pollution and meteorological factors from 1 January 2015 to 31 December 2016 were collected in Hefei, China. Time-series analysis was applied to assess the short-term effects of traffic-related air pollution on childhood AB outpatient visits. A Poisson generalised linear regression model combined with a distributed lag non-linear model was used to estimate the relationships, controlling for long-term trends, seasonal patterns, meteorological factors and other possible confounders. RESULTS: We found that an IQR increase in concentrations of nitrogen dioxide, particulate matter <2.5 µm and carbon monoxide significantly increased the daily hospital visits for childhood AB with 4-day cumulative effect estimates (relative risks: 1.03, 95% CI 1.01 to 1.05; 1.09, 95% CI 1.07 to 1.11; 1.07, 95% CI 1.05 to 1.09). Notably, the risk estimates during the cold season are pronounced; however, no significant association was observed during the warm season. Interestingly, children aged 6-14 years were more vulnerable to air pollutants than children aged less than 1 year and within 1-5 years. However, no gender difference was observed. CONCLUSION: A significant association of traffic-related air pollution and increased department visits for childhood AB was observed, notably in school-age children and during the cold season.

Arachidonic acid with taurine enhances pulmonary absorption of macromolecules without any serious histopathological damages.

Therapeutic peptides and protein are being used in several indications; however, their poor permeability still remains to be solved. This study focused on the pulmonary route of macromolecules. First, the effects of arachidonic acid (AA) as an absorption enhancer on drug serum concentration, after intratracheal administration, were investigated in rats. Second, the safety of AA was assessed in rats in an acute toxicity study for 7days. AA enhanced the exposure of both interferon-α (IFN-α) and fluorescein isothiocyanate 4000 (FD-4). In addition, the histopathological analysis indicated that AA caused alveolitis and bronchitis in rats. In combination with Taurine (Tau), these lung injuries were prevented through the histopathological analysis. The combined use of Tau with AA did not show any changes in the pharmacokinetics of FD-4. From these results, we suggest the combined use of AA with Tau as a novel formulation on the pulmonary route of macromolecule drugs. This formulation could improve the bioavailability of macromolecule drugs without any serious local damage to the lungs.

IMPACT OF SOME ENVIRONMENTAL FACTORS ON HUMAN HEALTH.

This paper presents statistical data of 2012-2015 on the diseases caused by the atmospheric air and water pollutions in Ajara region. The research on the content of dust, sulfur dioxide and nitrogen dioxide as well as carbon monoxide in the atmospheric air was held together with the National Environment Agency Ajara Monitoring Service. The results of the research have shown that the average content of the dust reached its maximum in 2012 (0.60 mg/m3) and it dropped to the minimum in 2015 (0.441 mg/m3). As for average content of carbon monoxide the maximum was observed in 2013 (3.1 mg/m3) and minimum in 2015 (2.1 mg/m3). Average content of the sulfur dioxide was at maximum in 2015 (0.159 mg/m3) and at minimum in 2012 (0.07 mg/m3). The average content of nitrogen dioxide reached its maximum in 2015 (0.153 mg/m3) and was found to be at its minimum in 2012 (0.13 mg/m3). In parallel statistical research of the registered diseases (chronic and undetermined bronchitis, asthma, allergic rhinitis and trachea/bronchi/lung malignant cancer) in Ajara during 2012-2015 has been performed. These diseases were especially common among the population over the age of 40. It may be concluded that in 2015 the cases of diseases caused by the atmospheric air pollution in Ajara have become more frequent compared to the previous years. Therefore, it is evident that monitoring of atmosphere air should be improved and corresponding preventive measures should be undertaken.