Effect of an Intranasal Corticosteroid on Quality of Life and Local Microbiome in Young Children With Chronic Rhinosinusitis: A Randomized Clinical Trial.

Importance: Intranasal corticosteroids (INCs) remain the first-line treatment of chronic rhinosinusitis (CRS) in both adults and children, despite the lack of evidence regarding their efficacy in the pediatric population. Similarly, their effect on the sinonasal microbiome has not been well documented. Objective: To assess the clinical, immunological, and microbiological effects of 12 weeks of an INC in young children with CRS. Design, Setting, and Participants: This open-label randomized clinical trial was performed in a pediatric allergy outpatient clinic in 2017 and 2018. Children aged 4 to 8 years with CRS diagnosed by a specialist were included. Data were analyzed from January 2022 to June 2022. Interventions: Patients were randomized to receive intranasal mometasone in an atomizer for 12 weeks (1 application per nostril, once per day) and supplemental 3-mL sodium chloride (NaCl), 0.9%, solution in a nasal nebulizer once a day for 12 weeks (INC group) or 3-mL NaCl, 0.9%, solution in a nasal nebulizer once a day for 12 weeks (control group). Main Outcomes and Measures: Measures taken both before and after treatment included the Sinus and Nasal Quality of Life Survey (SN-5), a nasopharynx swab for microbiome analysis by next-generation sequencing methods, and nasal mucosa sampling for occurrence of innate lymphoid cells (ILCs). Results: Of the 66 children enrolled, 63 completed the study. The mean (SD) age of the cohort was 6.1 (1.3) years; 38 participants (60.3%) were male and 25 (39.7%) were female. The clinical improvement reflected by reduction in SN-5 score was significantly higher in the INC group compared with the control group (INC group score before and after treatment, 3.6 and 3.1, respectively; control group score before and after treatment, 3.4 and 3.8, respectively; mean between-group difference, -0.58; 95% CI, -1.31 to -0.19; P = .009). The INC group had a greater increase in nasopharyngeal microbiome richness and larger decrease in nasal ILC3 abundance compared with the control group. A significant interaction was observed between change in microbiome richness and the INC intervention on the prediction of significant clinical improvement (odds ratio, 1.09; 95% CI, 1.01-1.19; P = .03). Conclusions and Relevance: This randomized clinical trial demonstrated that treatment with an INC improved the quality of life of children with CRS and had a significant effect on increasing sinonasal biodiversity. Although further investigation is needed of the long-term efficacy and safety of INCs, these data may reinforce the recommendation of using INCs as a first-line treatment of CRS in children. Trial Registration: ClinicalTrials.gov Identifier: NCT03011632.

Upper-airway dysbiosis related to frequent sweets consumption increases the risk of asthma in children with chronic rhinosinusitis.

BACKGROUND: Innate immunity response to local dysbiosis seems to be one of the most important immunologic backgrounds of chronic rhinosinusitis (CRS) and concomitant asthma. We aimed to assess clinical determinants of upper-airway dysbiosis and its effect on nasal inflammatory profile and asthma risk in young children with CRS. METHODS: We recruited one hundred and thirty-three children, aged 4-8 years with doctor-diagnosed CRS with or without asthma. The following procedures were performed in all participants: face-to-face standardized Sinus and Nasal Quality of Life questionnaire, skin prick test, taste perception testing, nasopharynx swab, and sampling of the nasal mucosa. Upper-airway dysbiosis was defined separately by asthma-specific microbiome composition and reduced biodiversity. Multivariate methods were used to define the risk factors for asthma and upper-airway dysbiosis and their specific inflammatory profile of nasal mucosa. RESULTS: The asthma-specific upper-airway microbiome composition reflected by the decreased ratio of Patescibacteria/Actinobacteria independently of atopy increased the risk of asthma (OR:8.32; 95%CI: 2.93-23.6). This asthma-specific microbiome composition was associated with ≥ 7/week sweet consumption (OR:2.64; 95%C:1.11-6.28), reduced biodiversity (OR:3.83; 95%CI:1.65-8.87), the presence of Staphylococcus strains in the nasopharynx (OR:4.25; 95%CI:1.12-16.1), and lower expression of beta-defensin 2, IL-5, and IL-13 in the nasal mucosa. The reduced biodiversity was associated with frequent antibiotic use and with a higher nasal expression of IL-17 and T1R3 (sweet taste receptor). In asthmatic children, reduced sweet taste perception was observed. CONCLUSIONS: Specific upper-airway dysbiosis related to frequent sweet consumption, frequent antibiotic courses, and altered nasal immune function increases the risk of asthma in young children with CRS.

Prevalence, risk factors and underdiagnosis of asthma in the general population aged over 60 years.

INTRODUCTION: Bronchial asthma is one of the frequent chronic diseases in elderly persons. Global data show that 6.5-17% of the elderly suffer from asthma. However, there are no Polish data available on asthma prevalence in this group. AIM: This article is a retrospective analysis of the Polish Multicentre Study of Epidemiology of Allergic Diseases (PMSEAD) results aimed at assessing prevalence and clinical characteristics in the elderly. MATERIAL AND METHODS: The study was conducted in 1998-1999 in 11 research centres in Poland, including the Lodz centre. The study included randomly selected subjects of both sexes. Demographics and prevalence were assessed among adults (aged 16-80 years) based on the nationwide database and the detailed clinical analysis was based on the Lodz centre database. RESULTS: Nationwide data were obtained from 12 970 adults, including 1057 respondents in the Lodz Province; 20.3% of respondents in Poland and 23.6% in the Lodz Province were over 60 years of age. In both groups, elderly participants significantly more frequently suffered from asthma (asthma prevalence in this group was 6.7% for Poland and 12.0% for the Lodz Province). The multivariate analysis demonstrated that age over 60 years (OR = 2.08), residence in the city centre (OR = 3.30), and occurrence of seasonal allergic rhinitis (OR = 3.11) were significant risk factors for asthma occurrence among the residents of the Lodz Province. Among the elderly in Lodz, almost 50% of patients with asthma had not had a proper diagnosis made despite reporting clinical symptoms. CONCLUSIONS: In Poland asthma is a common and frequently underdiagnosed disease in the elderly.

The position paper of the Polish Society of Allergology on climate changes, natural disasters and allergy and asthma.

The observed global climate change is an indisputable cause of the increased frequency of extreme weather events and related natural disasters. This phenomenon is observed all over the world including Poland. Moreover, Polish citizens as tourists are also exposed to climate phenomena that do not occur in our climate zone. Extreme weather events and related disasters can have a significant impact on people with allergic diseases, including asthma. These effects may be associated with the exposure to air pollution, allergens, and specific microclimate conditions. Under the auspices of the Polish Society of Allergology, experts in the field of environmental allergy prepared a statement on climate changes, natural disasters and allergy and asthma to reduce the risk of adverse health events provoked by climate and weather factors. The guidelines contain the description of the factors related to climate changes and natural disasters affecting the course of allergic diseases, the specific microclimate conditions and the recommendations of the Polish Society of Allergology for vulnerable population, patients suffering from asthma and allergy diseases, allergologists and authorities in the event of climate and weather hazards.

Occupational exposure to diisocyanates in polyurethane foam factory workers.

OBJECTIVES: The aim of the study was to evaluate health effects of occupational exposure to diisocyanates (DIC) among polyurethane foam products factory workers. MATERIAL AND METHODS: Thirty workers had a physical examination, skin prick tests with common allergens, allergen-specific immunoglobulin E (IgE) antibodies to diisocyanates and pulmonary function tests. Concentrations of selected isocyanates in the workplace air samples as well as concentration of their metabolites in the urine samples collected from the workers of the plant were determined. RESULTS: The most frequent work-related symptoms reported by the examined subjects were rhinitis and skin symptoms. Sensitization to at least 1 common allergen was noted in 26.7% of the subjects. Spirometry changes of bronchial obstruction of a mild degree was observed in 5 workers. The specific IgE antibodies to toluene diisocyanate (TDI) and 4,4'-methylenebis(phenyl isocyanate) (MDI) were not detected in any of the patients' serum. Cellular profiles of the collected induced sputum (ISP) did not reveal any abnormalities. Air concentrations of TDI isomers ranged 0.2-58.9 µg/m3 and in 7 cases they exceeded the Combined Exposure Index (CEI) value for those compounds. Concentrations of TDI metabolites in post-shift urine samples were significantly higher than in the case of pre-shift urine samples and in 6 cases they exceeded the British Biological Monitoring Guidance Value (BMGV - 1 µmol amine/mol creatinine). We didn't find a correlation between urinary concentrations of TDI, concentrations in the air and concentrations of toluenediamine (TDA) in the post shift urine samples. Lack of such a correlation may be an effect of the respiratory protective equipment use. CONCLUSIONS: Determination of specific IgE in serum is not sensitive enough to serve as a biomarker. Estimation of concentrations of diisocyanate metabolites in urine samples and the presence of work-related allergic symptoms seem to be an adequate method for occupational exposure monitoring of DIC, which may help to determine workers at risk as well as to recognize hazardous workplaces.

The prevalence of asthma work relatedness: Preliminary data.

OBJECTIVES: About 5-10% of asthmatics do not respond well to standard treatment plan. Occupational exposure may be one of the factors that can be linked with treatment failure. The aim of the study was to assess the prevalence of work-related asthma (WRA) among adult asthmatics under follow up in an outpatient allergy clinic and to create a useful tool for detecting individuals with possible WRA. MATERIAL AND METHODS: Preliminary 5-question questionnaire designed to recognize WRA was presented to 300 asthmatics. All patients with positive preliminary verification along with 50 subjects from control group were asked to fill up a detailed questionnaire. The WRA was diagnosed by positive match for asthma symptoms in combination with workplace exposure indicated in the detailed WRA questionnaire followed by confirmation of each WRA case by detailed exposure analysis. RESULTS: Work-related asthma was recognized in 63 subjects (21% of study group). The preliminary questionnaire has 76.9% sensitivity and 94% specificity in recognition of WRA. Occupational exposure to irritants is a risk factor of WRA recognition (relative risk (RR) = 2.09 (1.44:3.03)). Working in exposure-free environment is a factor against WRA recognition (RR = 0.38 (0.24:0.61)). Among subjects with work-related asthma, the uncontrolled course of the disease is significantly more frequent (p = 0.012). Subjects with WRA more often report sickness absenteeism due to asthma than those without WRA (9.6% vs. 3.2%, respectively), but the observed differences did not reach the statistical significance. CONCLUSIONS: Short 5-question questionnaire seems to be a promising tool to detect individuals with possible work-related asthma in the outpatient setting for further evaluation and additional attention.

Work-related symptoms among workers exposed to black tea dust.

BACKGROUND: Tea may be classified as unfermented green, semi-ferinented oolong and fermented black. All of these types are derived from Camellia sinensis, the Tea Plant, which contains the low molecular weight (LMW) agent Epigallocatechin gallate (EGCg), probably responsible for allergic reactions. The aim of our study was to asses the work-related allergic symptoms and IgE-mediated sensitivity among black tea packers. MATERIAL AND METHODS: Study groups comprised 26 black tea packers (group 1) and 20 office workers (group 2). A questionnaire, skin prick tests (SPTs) to common allergens and black tea, evaluation of specific IgE (asIgF) to Camellia sinensis and moulds, pre- and post-work-shift spirometry were performed. RESULTS: At least I symptom suggesting allergic disease was reported by 85% of the tea packers and 60% of the office workers. The most frequent positive results of SPTs were obtained with moulds (8%). A small decline in FE%1 (forced expiratory volume in I s) after the work shift was observed among tea packers sensitized to moulds. CONCLUSIONS: Although specific sensitization to black tea was not observed in our study groups, cough and skin symptoms were significantly more frequently among the tea packers than in office workers. The irritant impact on the airways and the skin of tea dust and/or sensitization to moulds contaminating tea leaves are being suspected.

Occupational asthma caused by samba (Triplochiton scleroxylon) wood dust in a professional maker of wooden models of airplanes: a case study.

OBJECTIVES: Wood dust is a known occupational allergen that may induce, in exposed workers, respiratory diseases including asthma and allergic rhinitis. Samba (obeche, Triplochiton scleroxylon) is a tropical tree, which grows in West Africa, therefore, Polish workers are rarely exposed to it. This paper describes a case of occupational asthma caused by samba wood dust. MATERIAL AND METHODS: The patient with suspicion of occupational asthma due to wood dust was examined at the Department of Occupational Diseases and Clinical Toxicology in the Nofer Institute of Occupational Medicine. Clinical evaluation included: analysis of occupational history, skin prick tests (SPT) to common and occupational allergens, determination of serum specific IgE to occupational allergens, serial spirometry measurements, metacholine challenge test and specific inhalation challenge test with samba dust RESULTS: SPT and specific serum IgE assessment revealed sensitization to common and occupational allergens including samba. Spirometry measurements showed mild obstruction. Metacholine challenge test revealed a high level of bronchial hyperactivity. Specific inhalation challenge test was positive and cellular changes in nasal lavage and induced sputum confirmed allergic reaction to samba. CONCLUSIONS: IgE mediated allergy to samba wood dust was confirmed. This case report presents the first documented occupational asthma and rhinitis due to samba wood dust in wooden airplanes model maker in Poland.

Work-related respiratory symptoms among health centres cleaners: a cross-sectional study.

OBJECTIVES: Several studies, mostly based on questionnaire-derived data, have shown an increased risk of allergic diseases, especially asthma, among cleaners. The risk factors and etiological mechanisms are still being investigated. Occupational exposure to various chemical and biological agents may induce specific sensitization and/or irritant effects. The aim of our study was to estimate the prevalence of work-related symptoms suggesting the presence of allergic disease reported by cleaners, and to relate them to the results of commercially available and standardized objective tests used for screening detection of occupational sensitization and chronic respiratory disorders. MATERIAL AND METHODS: A cross-sectional study was performed among 142 Polish workers of cleaning service in their workplaces. A detailed questionnaire, skin prick tests to common allergens and chemicals used by these workers for cleaning purposes (chloramine T, chlorhexidine, formaldehyde, glutaraldehyde, benzalconium chloride), total and specific serum IgE antibodies to disinfectants and rest spirometry were performed in all the subjects. RESULTS: Fifty nine percent of all the subjects declared occurrence of at least 1 symptom suggesting allergic ailment during cleaning activities at work. Skin prick tests and specific serum IgE antibodies to disinfectants were negative in all the subjects. In 8 cases wheezing was detected during auscultation, but only in 5 of them obstructive pattern in rest spirometry was found. CONCLUSIONS: Occupational allergic causation of symptoms among cleaners could be less likely than work-related symptoms associated with exacerbations of new-onset or pre-existing respiratory diseases. Therefore, in this group of workers, mainly the non-specific irritant impact of chemicals on airways should be taken into consideration.

Effect of inhaled toluene diisocyanate on local immune response based on murine model for occupational asthma.

Highly reactive, low-molecular-weight diisocyanates (DIC) are the most commonly identified cause of occupational asthma (OA). Animal/clinical studies of DIC asthma have been more limited compared with atopic asthma, and an understanding of DIC pathogenesis is less clear. The aim of this study was to investigate in a mouse model, toluene diisocyanate (TDI, as 2,4-TDI isomer)-induced inflammatory reactions/cytokine profile changes in the lungs and accompanying changes in lymph node lymphocyte sub-populations. The study used female BALB/cJ/Han/IMP mice that were exposed first intra-nasally and then in an inhalation chamber to TDI or air. After the final exposure, bronchoalveolar lavage fluid (BALF) was collected and changes induced in inflammatory cell composition, levels of key cytokines (i.e. IL-4, TNFα, IFNγ), and lymphocyte sub-population profiles within auricular lymph nodes, were evaluated. Total number of cells in the BALF of treated mice was significantly higher than in control mice BALF. There was also a significant increase in BALF neutrophil and eosinophil levels with TDI mice compared to in controls; lymphocyte and macrophage numbers did not significantly differ. A significant increase in BALF levels of TNFα and IFNγ was also noted in mice exposed to TDI relative to levels in controls. BALF IL-4 levels were also increased, but the change from control was not significant. Lastly, the levels/percentages of CD3(+)CD4(+) (T-helper [TH]) lymphocytes significantly increased in the lymph nodes of TDI-exposed groups while those of the CD3(+)CD8(+) cells decreased as compared to in control mice. These studies, the first to assess TDI-induced changes in levels of three key cytokines in BALF in conjunction with changes in local lymph nodes following first an intra-nasal and then a general inhalation exposure to a low-level of TDI, confirm that TDI inhalation induces a pathology manifested by airway inflammation, TH cell-derived cytokine production, and shifts in lymph node lymphocytes sub-populations toward increases in TH cells.

Mould sensitisation among bakers and farmers with work-related respiratory symptoms.

Fungi belong to common allergens, which can be found both in occupational and non-occupational environment. The aim of the study was to determine the frequency and factors associated with mould allergy among bakers and farmers reporting work-related respiratory symptoms. The study group comprised 117 bakers and 83 farmers reporting work-related respiratory symptoms. Skin prick tests (SPT) with common, fungal and occupational allergens, estimation of serum total IgE level, spirometry, histamine test and specific inhalative challenge test with occupational allergens were performed in all subjects. The prevalence of hypersensitivity to fungal species was higher among farmers (32.5%) than bakers (16.2%). Positive SPT with mould allergens were found among 10.8% farmers and 6.8% bakers with occupational allergy. The fungi allergens giving positive SPT results most frequently were Candida albicans, Levures mélanges, Aspergillus mix. and Charbons cerealiers in both groups. Among mould allergens, hypersensitivity to Aspergillus genus was the most common in farmers and bakers group, while among Saccharomyces - Candida albicans sensitization was the most frequently detected. Mould hypersensitivity is related to occupational respiratory allergy, especially to asthma and rhinitis in farmers, and occupational asthma in bakers. Although sensitization to Saccharomyces was more frequent, similar correlation was not observed.

Immunological determinants in a murine model of toluene diisocyanate-induced asthma.

OBJECTIVES: Diisocyanates (DIC) are highly reactive, low-molecular-weight chemicals which are the leading cause of occupational asthma (OA). The aim of the study was to analyze certain aspects of the pathogenesis of allergic inflammation in the airways induced by toluene diisocyanate (TDI) in an experimental model in mice. MATERIALS AND METHODS: The experiment was carried out on 50 female BALB/cJ/Han/IMP mice, which were exposed by inhalation (intranasal and in the inhalation chamber) to toluene diisocyanate (2,4-TDI). After the experiment, the bronchoalveolar lavage fluid (BALF) was collected from the animals, and the composition of the induced inflammatory cells, and the concentrations of certain cytokines (IL-4, IL-5, TNF-α) were evaluated. RESULTS: The total number of cells in BALF of the examined group of mice was significantly higher compared to the control mice. There was also a significant increase in neutrophils and eosinophils in the study group compared to the controls. The number of lymphocytes and macrophages did not differ significantly between the two groups. A statistically significant increase in the level of TNF-α was shown to occur in the group exposed to toluene diisocyanate in comparison to the control group. The concentration of IL-4 increased in the study group, compared to the control one, but the differences did not reach the level of significance, p > 0.05. Such difference was not observed for IL-5. CONCLUSIONS: We developed a murine model of TDI-induced asthma which caused the influx of inflammatory cells like eosinophils and neutrophils in the bronchoalveolar lavage fluid (BALF) in the TDI-treated mice. The increase of the concentration of some proinflammatory cytokines (TNF-α, IL-4) in BALF from the exposed mice was also observed.

[Borreliosis in occupational medicine practice]. / Borelioza w praktyce lekarza medycyny pracy.

Lyme borreliosis is a multisystem infectious disease that can occur from bites by infected ticks. It can appear at persons exposed professionally for staying in tick feeding environment as well as persons staying in such an environment occasionally. For a few years the Lyme disease is taking the leading place amongst occupational diseases and first amongst infectious occupational diseases. Lyme disease is a major problem especially in wooded areas of Poland however it can occur throughout the country. The variety of clinical and serological pictures is creating everyday diagnostic problems. The aim of this publication is to collect, methodize and remind the medical knowledge about pathogenesis, symptoms, diagnostics, prevention and medical certification of this disease. Disease symptoms were specified to appearing in various organs and systems in order to clarify this difficult to diagnose disease. Diagnostics of Lyme disease was divided into standard and highly specialized, performed in special cases.

[Pathogenetic and clinical aspects of diisocyanate asthma]. / Wybrane patogenetyczne i kliniczne aspekty astmy wywolanej zawodowa ekspozycja na diizocyjaniany.

Diisocyanates are currently the most common cause of occupational asthma in industrialized countries, where its prevalence ranges from less than 5% to 15%. They are mainly used in the production of polyurethane foam, plastic packagings, laminates and polyurethane paints. The diagnosis of diisocyanate asthma is often problematic due to the lack of simple diagnostic or screening tests, uncertainty of underlying mechanisms, and a multitude of other potential occupational and environmental causes of asthma. At present, only a specific standardized challenge test with diisocyanates in concentrations not exceeding the adopted hygiene standards has been found to show a real diagnostic value. The diisocyanate-inducedsensitization, is associated with the recruitment of CD4 T lymphocytes to the lungs and the production of Th2-type cytokines, including IL-4, IL-5 and IL-13. However, clinical studies have suggested that an immunological response to diisocyanates may involve both Th1 and Th2 cells. The development of animal models has been instrumental in furthering the understanding of the pathogenesis of many diseases, including bronchial asthma. Murine models of diisocyanate-induced asthma have proved to be the most useful. Mouse models offer distinct advantages of a better-defined genome than that of guinea pigs or rats and the availability of antibody reagents and transgenic strains to investigate detailed mechanistic pathways. A better understanding of the immunopathogenesis of diisocyanate asthma will hopefully lead to early markers of sensitization and asthma, as well as to a profound comprehension of exposure and host risk factors, both of them should greatly facilitate the development of much-needed diagnostic and preventive strategies for diisocyanate asthma.

Metal-induced asthma and chest X-ray changes in welders.

OBJECTIVES: The aim of this study was to evaluate the coexisting factors and usefulness of diagnostic methods in metal-induced asthma in Polish welders. MATERIALS AND METHODS: Examination of 50 welders occupationally exposed to metals and with suspicion of metal-induced asthma (group A), 100 welders occupationally exposed to metals but without suspicion of metal-induced asthma (group B), and two control groups (10 patients with atopic asthma and 10 healthy subjects) was carried out. Questionnaire survey, clinical examination, skin prick tests to common aeroallergens and metal salts, rest spirometry tests, X-ray, metacholine challenge and a single-blind, placebo controlled specific inhalation challenge tests with metals (or work-like conditions challenge tests) were performed. RESULTS: In group A--in 9 cases we obtained positive results of specific inhalation challenge tests with metals (in 3 cases with nickel, in 4 cases with chromium, in 1 case with cobalt and in 1 case with manganese). Nine cases of metal-induced occupational asthma were recognized. In group B--only in one case we obtained positive results of work-like conditions challenge test (clinical and spirometry changes, eosinophil influx in induced sputum), which confirmed the diagnosis of occupational asthma. In most of examined welders (62%), pulmonary changes in chest X-ray images were noted. The statistical analysis revealed that working as a welder for more than 10 years is the coexisting factor of presence of chest X-ray changes (p- or q-type nodular changes or interstitial changes). Positive results of skin prick tests with metal salts were the coexisting factors of occupational asthma due to metals among examined group of welders. CONCLUSIONS: Specific inhalation challenge plays the key role in diagnostics of metal-induced asthma in welders. Pulmonary changes in chest X-ray were found in a significant percentage of examined welders.

Contact blepharoconjunctivitis due to black henna--a case report.

Para-phenylenediamine (PPD) can induce immediate or - more often - delayed hypersensitivity. We report the case of 48-year old female admitted to the out-patient allergy clinic a day after her visit in a beauty parlour, where she had her eyelashes and eyebrows dyed with henna. Physical examination revealed prominent edema of the upper part of the face including forehead, cheeks and eyes causing severe narrowing of the palpebral chink. Skin prick tests (SPT) with common allergens were positive for Dermatophagoides pteronyssinus, Dermatophagoides farinae and moulds, while the SPT with PPD was negative. Patch test to PPD was positive. Further investigations revealed eosinophilia in the tear fluid. To our knowledge, this is the first case of PPD-induced contact blepharoconjunctivitis (CB) with concomitant increased eosinophilia in the tear fluid.