Breathlessness and "exacerbation" questions predictive for incident COPD (MARKO study): data after two years of follow-up.

Aims: To determine the predictability of the MARKO questionnaire and/or its domains, individually or in combination with other markers and characteristics (age, gender, smoking history, lung function, 6-min walk test (6 MWT), exhaled breath temperature (EBT), and hsCRP for the incident chronic obstructive pulmonary disease (COPD) in subjects at risk over 2 years follow-up period). Participants and Methods: Patients, smokers/ex-smokers with >20 pack-years, aged 40-65 years of both sexes were recruited and followed for 2 years. After recruitment and signing the informed consent at the GP, a detailed diagnostic workout was done by the pulmonologist; they completed three self-assessment questionnaires-MARKO, SGRQ and CAT, detailed history and physical, laboratory (CBC, hsCRP), lung function tests with bronchodilator and EBT. At the 2 year follow-up visit they performed: the same three self-assessment questionnaires, history and physical, lung function tests and EBT. Results: A sample of 320 subjects (41.9% male), mean (SD) age 51.9 (7.4) years with 36.4 (17.4) pack-years of smoking was reassessed after 2.1 years. Exploratory factor analysis of MARKO questionnaire isolated three distinct domains (breathlessness and fatigue, "exacerbations", cough and expectorations). We have determined a rate for incident COPD that was 4.911/100 person-years (95% CI [3.436-6.816]). We found out that questions about breathlessness and "exacerbations", and male sex were predictive of incident COPD after two years follow-up (AUC 0.79, 95% CI [0.74-0.84], p < 0.001). When only active smokers were analyzed a change in EBT after a cigarette (ΔEBT) was added to a previous model (AUC 0.83, 95% CI [0.78-0.88], p < 0.001). Conclusion: Our preliminary data shows that the MARKO questionnaire combined with EBT (change after a cigarette smoke) could potentially serve as early markers of future COPD in smokers.

Nasal Nitric Oxide in Children: A Review of Current Outreach in Pediatric Respiratory Medicine.

Nasal nitric oxide (nNO) is a gas synthesized by the inducible and constitutive NO synthase (NOS) enzyme in the airway cells of the nasal mucosa. Like lung nitric oxide, it is thought to be associated with airway inflammation in various respiratory diseases in children. The aim of our review was to investigate the current state of use of nNO measurement in children. A comprehensive search was conducted using the Web of Science and PubMed databases specifically targeting publications in the English language, with the following keywords: nasal NO, children, allergic rhinitis, chronic rhinosinusitis, acute rhinosinusitis, primary ciliary dyskinesia (PCD), and cystic fibrosis (CF). We describe the use of nNO in pediatric allergic rhinitis, chronic rhinosinusitis, acute rhinosinusitis, PCD, and CF based on the latest literature. nNO is a noninvasive, clinically applicable test for use in pediatric allergic rhinitis, chronic rhinosinusitis, acute rhinosinusitis, PCD, and CF. It can be used as a complementary method in the diagnosis of these respiratory diseases and as a monitoring method for the treatment of allergic rhinitis and acute and chronic rhinosinusitis.

Protocol Development of a Personalized Balanced Nutrition Concept for Preschool Children, Primarily Those with Food Allergies, Using an IT Platform.

Children with food allergies are at higher risk for severe anaphylactic reactions and for key nutrient deficiency. In order to address these concerns, enable early detection, and improve the monitoring of children with food allergies, an innovative IT platform will be developed by IT experts (IN2 Ltd. Zagreb, Croatia, part of Constellation Software Inc. (Toronto, ON, Canada)) and Srebrnjak Children's Hospital, Zagreb, Croatia (SCH) for the effective implementation of personalized balanced nutrition in preschool institutions in Croatia. Additionally, the data obtained through this research, including epidemiological data on allergic diseases, clinical data (diagnostic allergy tests and others), anthropometry, and physical activity status, will be used to create a national Allergy registry. Other than being a tool for personalized and balanced nutrition for children, especially those with special dietary requirements (including food allergy and intolerance), the IT platform developed in this study will enable the continuous monitoring of these children as a part of their clinical management plan and earlier detection of food allergies, intolerance, and other conditions, even outside of the healthcare system. This research also aims at optimizing current and developing novel personalized therapeutic regimes, detecting novel early biomarkers in children with food allergies and intolerances, and involving all key stakeholders (caregivers, preschool institutions, etc.) in the shared-care approach in the management of food allergies in children.

Validation of the fractional exhaled breath temperature measurement: reference values.

Exhaled breath temperature (EBT) is a known biomarker of inflammation and airways blood flow. As opposed to previous studies, we were able to measure temperature of separate fractions of exhaled breath (fEBT) (those from the peripheral and central airways). The aim was to validate the fEBT measurement method to determine the reference values and the influence of endogenous and exogenous factors on fEBT in healthy subjects. This cross-sectional study included 55 healthy adults in whom fEBT was repeatedly measured, two days in a row, using a FractAir®device. Also, basal metabolic rate, level of physical activity, distance from the main road, outdoor and ambient temperature, air pressure and humidity, haematology and inflammation markers, lung function, cumulative EBT and body temperature at characteristic points on the body were measured. The results showed that fEBT from central airways was lower compared to fEBT from the periphery and that fEBTs were not related to body temperature (p> 0.05 for all). We also showed repeatability of fEBT measurements for two consecutive days. All EBT fractions correlated significantly with ambient temperature (<0.01). No associations of fEBT with other personal and external factors were found using multivariate analysis. At room temperature of 22 °C, the physiological temperature values of the first fraction were 23.481 ± 3.150 °C, the second fraction 26.114 ± 4.024 °C and the third fraction 28.216 ± 3.321 °C. The proposed reference values represent the first part of validation of fEBT as the method for the use in clinical practice.

Atopic March or Atopic Multimorbidity-Overview of Current Research.

The atopic march encompasses a sequence of allergic conditions, including atopic dermatitis, food allergy, allergic rhinitis, and asthma, that frequently develop in a sequential pattern within the same individual. It was introduced as a conceptual framework aimed at elucidating the developmental trajectory of allergic conditions during childhood. Following the introduction of this concept, it was initially believed that the atopic march represented the sole and definitive trajectory of the development of allergic diseases. However, this perspective evolved with the emergence of new longitudinal studies, which revealed that the evolution of allergic diseases is far more intricate. It involves numerous immunological pathological mechanisms and may not align entirely with the traditional concept of the atopic march. The objective of our review is to portray the atopic march alongside other patterns in the development of childhood allergic diseases, with a specific emphasis on the potential for a personalized approach to the prevention, diagnosis, and treatment of atopic conditions.

Diagnosing Single and Multiple Drug Hypersensitivity in Children: A Tertiary Care Center Retrospective Study.

Drug hypersensitivity reactions (DHRs) are a type of adverse drug reactions with heterogeneous pathophysiological mechanisms and a broad spectrum of clinical manifestations. Since over-diagnosing is common in children, a complete allergy work-up is needed. A cross-sectional study was conducted at a tertiary care institution, covering the five-year period. Five hundred and four patients of both sexes, mean age 7.5 and with a medical history suggestive of DHR were evaluated. ENDA/EAACI guidelines were used for a diagnostic algorithm. Single drug hypersensitivity was registered in 375 patients and multiple drug hypersensitivity in 129. The main culprits in medical history were antibiotics (83%), non-steroidal anti-inflammatory drugs (NSAIDs) (8.4%) and analgoantipyretics (3.8%). Skin involvement was registered in 96.2%. DHRs were confirmed in 4.4% patients-six patients had positive skin tests and 13 had a positive drug provocation test. In the proven DHRs group, the main agents were antibiotics (72.7%), followed by NSAIDs (8.3%), and of all the skin manifestations, urticaria was most common (78.2%), followed by exanthema (10.5%) and angioedema (5.3%). Considering the above, anticipating DHRs and a proper referral of children to an allergologist is a key step in the assessment of drug hypersensitivity. A complete allergy work-up prevents unnecessary drug exclusion and allows most children to safely continue the use of first-line medications when needed.

Pseudophakic Cystoid Macular Oedema (PCME) Prevention in Patients with Non-Proliferative Diabetic Retinopathy (NPDR)-Randomized Controlled Trial.

Background and Objectives: The purpose of this study was to compare the effect of topical bromfenac and dexamethasone on the intraocular concentration of interleukin 6 (IL-6) and incidence of pseudophakic cystoid macular oedema (PCME) after cataract surgery in patients with non-proliferative diabetic retinopathy (NPDR). Materials and Methods: Ninety eyes of patients with mild-to-moderate NPDR that underwent phacoemulsification cataract surgery were divided into three groups. A detailed description of the clinical study protocol is described later in paper. In short, Group 1 received topical bromfenac (0.9 mg/mL), Group 2 dexamethasone (1 mg/mL), and Group 3 placebo, both preoperatively and postoperatively. Additionally, all patients received combined topical steroid and antibiotic drops (dexamethasone, neomycin and polymyxin B) 3 weeks postoperatively. On the day of the surgery, aqueous humour samples (0.1-0.2 mL) were obtained and IL-6 concentrations were analysed. Central foveal subfield thickness (CFT) measured using spectral-domain optical coherence tomography (SD-OCT) was analysed preoperatively and postoperatively. Results: There was no significant difference in IL-6 concentrations between groups. Postoperative CFT was significantly lower in the dexamethasone group compared to the placebo group. In addition, the correlation between IL-6 and CFT was statistically significant in the dexamethasone group. No patient developed PCME in any of the three groups. No adverse events were reported during the study. Conclusion: Topical bromfenac and dexamethasone have no significant effect on intraocular IL-6 concentration in patients with NPDR. Topical bromfenac is not more effective than topical dexamethasone in reducing postoperative CFT in patients with NPDR.

Diagnostic and Practical Value of Abbreviated Contrast Enhanced Magnetic Resonance Imaging in Breast Cancer Diagnostics.

BACKGROUND: Although MRI is the most efficient method of detecting breast cancer, its standard protocol is time-consuming and expensive. The objective of this study was to compare the diagnostic accuracy of the modified innovative abbreviated MRI protocol (AMRP) and the standard magnetic resonance protocol (SMRP) when detecting breast cancer. METHODS: The research involved 477 patients referred for breast MRI due to suspected lesions. They were randomly assigned to the AMRP group (N = 232) or the SMRP group (N = 245). The AMRP comprised one native (contrast-free) and four post-contrast dynamic sequences of T1-weighted volume imaging for breast assessment (VIBRANT) and 3d MIP (maximum intensity projection) lasting for eight minutes. All the patients underwent a core biopsy of their lesions and histopathological analysis. RESULTS: The groups were comparable regarding the pre-screening and post-diagnostic characteristics and were of average (±SD) age at breast cancer diagnosis of 53.6 ± 12.7 years. There was no significant difference between the two protocols in terms of specificity or sensitivity of breast cancer diagnosis. The sensitivity (95% Cis) of the AMRP was 99.05% (96.6-99.9%), and its specificity was 59.09% (36.4-79.3%), whereas the sensitivity of the SMRP was 98.12% (95.3-99.5%) and its specificity was 68.75% (50.0-83.9%). Most of the tumors comprised one solid lesion in one of the breasts (77.3%), followed by multicentric tumors (16%), bilateral tumors (4.3%), and multifocal tumors (1.7%). The average size of tumors was approximately 14 mm (ranging from 3 mm to 72 mm). CONCLUSION: Our innovative AMR protocol showed comparable specificity and sensitivity for the diagnosis of breast cancer when compared to SMRP, which is the "gold standard" for histopathological diagnosis. This can lead to great savings in terms of the time and cost of imaging and interpretation.

Anabolic androgenic steroid-induced liver injury: An update.

Anabolic androgenic steroids (AASs) are a group of molecules including endogenous testosterone and synthetic derivatives that have both androgenic and anabolic effects. These properties make them therapeutically beneficial in medical conditions such as hypogonadism. However, they are commonly bought illegally and misused for their anabolic, skeletal muscle building, and performance-enhancing effects. Supraphysiologic and long-term use of AASs affects all organs, leading to cardiovascular, neurological, endocrine, gastrointestinal, renal, and hematologic disorders. Hepatotoxicity is one of the major concerns regarding AASs treatment and abuse. Testosterone and its derivatives have been most often shown to induce a specific form of cholestasis, peliosis hepatis, and hepatic benign and malignant tumors. It is currently believed that mechanisms of pathogenesis of these disorders include disturbance of antioxidative factors, upregulation of bile acid synthesis, and induction of hepatocyte hyperplasia. Most toxicity cases are treated with supportive measures and liver function normalizes with discontinuation of AAS. However, some long-term consequences are irreversible. AAS-induced liver injury should be taken in consideration in patients with liver disorders, especially with the increasing unintentional ingestion of supplements containing AAS. In this paper, we review the most current knowledge about AAS-associated adverse effects on the liver, and their clinical presentations, prevalence, and pathophysiological mechanisms.

PRISM III Score Predicts Short-Term Outcome in Children with ARDS on Conventional and High-Frequency Oscillatory Ventilation.

Therapeutic recommendations for pediatric acute respiratory distress syndrome (PARDS) include conventional (CMV) and rescue high-frequency oscillatory mode (HFOV) of mechanical ventilation (MV). The pediatric risk of mortality (PRISM) is a frequently used mortality score for critically ill patients. In search of methods to recognize those patients, we analyzed the PRISM III score as a potential predictor of the short-term outcome in MV subjects with PARDS. A retrospective five-year study of PARDS in children on MV was conducted in the Pediatric ICU. Seventy patients were divided into two groups (age group <1 year and age group 1−7 years). The PRISM III score was used to assess the 28-day outcome and possible development of complications. The most common causes of PARDS were pneumonia and sepsis. Male sex, malnourishment, sepsis, and shock were significant indicators of poor outcome. The PRISM III score values were significantly higher in those who died, as well as in subjects requiring HFOV. The score had a significant prognostic value for short-term mortality. There was no significant difference in outcome based on the comparison of two modes of ventilation. A significantly higher score was noted in subjects who developed sepsis and cardiovascular insufficiency. The PRISM III score is a fair outcome predictor during the 28-day follow-up in MV subjects with PARDS, regardless of the ventilation mode.

Third-Day Oxygenation Index is an Excellent Predictor of Survival in Children Mechanically Ventilated for Acute Respiratory Distress Syndrome.

PURPOSE: The aim of this study was to assess the association between oxygenation index (OI) and outcome in children with acute respiratory distress syndrome (ARDS). PATIENTS AND METHODS: Patients (age, >30 days) in the pediatric intensive care unit from April 2011 to March 2016 with ARDS and who were mechanically ventilated were included. Patients were divided into two age groups: infants (<12month) and older children. Lowest PaO2/FiO2 and SpO2/FiO2 ratios and highest mean airway pressure (MAP) were recorded on the first day of ARDS and after 72 h. OI was calculated on the first and third days of mechanical ventilation (MV) and its association with OI (first and third days) and short-term mortality evaluated at 28 days. RESULTS: MV was initiated a mean of 2.3 days after admission (median, 1.0 day; maximum 14 days). The average MV duration for all patients was 11.8 (median, 7.0) days. Mean (95% confidence interval (CI)) OI values on the first day of MV were 14.17 (11.94-16.41), 12.72 (10.68-14.75), and 13.24 (11.73-14.74) for infants, older children, and all participants, respectively. In survivors (n=39) mean OI was 11.66 (9.64-13.68) compared with 15.22 (13.03-17.40) in non-survivors (n=31). Logistic regression analysis revealed that OI on day 3 had highly significant prognostic value for mortality (odds ratio, 256.5, 95% CI 27.1-2424, p<0.001), with an AUC of 0.919 (cut-off value, 17; positive predictive value, 0.905; negative predictive value, 0.964; p=0.0001). In contrast, OI on day 1 did not have significant prognostic value (AUC, 0.634; p=0.056) for short-term mortality. Different modes of MV were not significantly associated with outcome (p>0.05). CONCLUSION: OI is a simple, highly accurate, and sensitive predictor of the survival (short-term mortality) of children mechanically ventilated for ARDS.

Medical devices in allergy practice.

Medical devices provide people with some health benefits in terms of diagnosis, prevention, treatment, and monitoring of disease processes. Different medical specialties use varieties of medical devices more or less specific for them. Allergology is an interdisciplinary field of medical science and teaches that allergic reactions are of systemic nature but can express themselves at the level of different organs across the life cycle of an individual. Subsequently, medical devices used in allergology could be regarded as: 1) general, servicing the integral diagnostic and management principles and features of allergology, and 2) organ specific, which are shared by organ specific disciplines like pulmonology, otorhinolaryngology, dermatology, and others. The present position paper of the World Allergy Organization (WAO) is meant to be the first integral document providing structured information on medical devices in allergology used in daily routine but also needed for sophisticated diagnostic purposes and modern disease management. It is supposed to contribute to the transformation of the health care system into integrated care pathways for interrelated comorbidities.

Expiratory variability index (EVI) is associated with the severity of acute bronchial obstruction in small children: A proof-of-concept study.

BACKGROUND: Lung function testing in small children is cumbersome. However, reduced variability of tidal breathing recorded using impedance pneumography (IP) during sleep was recently found to be a potential objective marker of wheeze in children aged 1-5 years. We aimed to investigate how an acute bronchial obstruction (BO) and its severity, and recovery thereof reflect in expiratory variability index (EVI). METHODS: EVI was measured using a wearable IP system (Ventica®) during sleep in 40 healthy controls (aged 1.5-5.9 years) and 30 patients hospitalized due to acute BO (aged 1.3-5.3 years). In healthy controls, EVI was measured for 1-3 nights at their homes. Patients were measured for several nights during hospitalization, as practically feasible, and at home 2 and 4 weeks post-discharge. RESULTS: We received 79 EVI results from 39 controls and 139 from 30 patients. 90% had previous BO episodes, 30% used asthma controller medication before and 100% after hospitalization. Compared to controls, EVI was significantly lower during hospitalization (P < .0001) having significant correlation with number of days to discharge (r = -.38, P = .004). At 2 or 4 weeks post-discharge, EVI was not significantly different from the controls (P = .14, P = .49, respectively). EVI was significantly associated with chest auscultation findings (P = .0001) being 17.5 (4.9) (median, IQR) with normal auscultation, 15.6 (7.4) in those with prolonged expiration and 11.4 (6.8) in those with wheeze and/or rales and crackles. CONCLUSIONS: EVI was found to be a sensitive, objective marker of acute BO, showing strong association with changes in clinical status in wheezy children aged 1-5 years.

Association of bacterial load in drinking water and allergic diseases in childhood.

BACKGROUND: Treatment of drinking water may decrease microbial exposure. OBJECTIVE: To investigate whether bacterial load in drinking water is associated with altered risk of allergic diseases. METHODS: We recruited 1,110 schoolchildren aged 6-16 years between 2011 and 2013 in Pozega-Slavonia County in Croatia, where we capitalized on a natural experiment whereby individuals receive drinking water through public mains supply or individual wells. We obtained data on microbial content of drinking water for all participants; 585 children were randomly selected for more detailed assessments, including skin prick testing. Since water supply was highly correlated with rural residence, we compared clinical outcomes across four groups (Rural/Individual, Rural/Public, Urban/Individual and Urban/Public). For each child, we derived quantitative index of microbial exposure (bacterial load in the drinking water measured during the child's first year of life). RESULTS: Cumulative bacterial load in drinking water was higher (median [IQR]: 6390 [4190-9550] vs 0 [0-0]; P < .0001), and lifetime prevalence of allergic diseases was significantly lower among children with individual supply (5.5% vs 2.3%, P = .01; 14.4% vs 6.7%, P < .001; 25.2% vs 15.1%, P < .001; asthma, atopic dermatitis [AD] and rhinitis, respectively). Compared with the reference group (Urban/Public), there was a significant reduction in the risk of ever asthma, AD and rhinitis amongst rural children with individual supply: OR [95% CI]: 0.14 [0.03,0.67], P = .013; 0.20 [0.09,0.43], P < .001; 0.17 [0.10,0.32], P < .001. Protection was also observed in the Rural/Public group, but the effect was consistently highest among Rural/Individual children. In the quantitative analysis, the risk of allergic diseases decreased significantly with increasing bacterial load in drinking water in the first year of life (0.79 [0.70,0.88], P < .001; 0.90 [0.83,0.99], P = .025; 0.80 [0.74,0.86], P < .001; current wheeze, AD and rhinitis). CONCLUSIONS AND CLINICAL RELEVANCE: High commensal bacterial content in drinking water may protect against allergic diseases.

Sources of variability in expiratory flow profiles during sleep in healthy young children.

Standard lung function tests are not feasible in young children, but recent studies show that the variability of expiratory tidal breathing flow-volume (TBFV) curves during sleep is a potential indirect marker of lower airway obstruction. However, the neurophysiological sources of the TBFV variability in normal subjects has not been established. We investigated sleep stages and body position changes as potential sources for the TBFV curve variability. Simultaneous impedance pneumography (IP), polysomnography (PSG) and video recordings were done in 20 children aged 1.4-6.9 years without significant respiratory disorders during sleep. The early part of expiratory TBFV curves are less variable between cycles of REM than NREM sleep. However, within individual sleep cycles, TBFV curves during N3 are the least variable. The differences in TBFV curve shapes between sleep stages are the main source of overnight variability in TBFV curves and the changes in body position have a lesser impact.

Fraction of air coming from conductive airways has the negative balance in heat dissipation after maximal effort exercise-a physiological basis for exercise-induced bronchoconstriction.

Exhaled breath temperature (EBT) has recently been used as a tool to assess the level of inflammation in airways. The newest technology can also assess EBT coming from different fractions of exhaled air (fEBT). We aimed to assess the changes in fEBT after a maximal cardio-pulmonary exercise test in healthy athletes. Forty-four healthy professional athletes (two females) were included. Their mean (±SD) age was 22.9 ± 4.8 years. An innovative device (FractAir®) was used for fEBT measurement, dividing the exhaled air into three fractions (V1, V2 and V3) coming from different parts of the lungs; the large airways (anatomic dead space), conductive airways (functional dead space) and the peripheral part. For V3 an EBT point measured at 1200 ml of exhaled volume was used to obtain the information about the distant parts of the lungs while eliminating the difference in the volume of total exhaled air before and after the exercise. The difference (temperature gain) between the starting and peak EBT for each fraction was also calculated. The peak fEBT values before and after exercise did not differ significantly (p > 0.05 for all three fractions). Temperature gain analysis for each fEBT showed a significant fall after exercise for V2 (1.71 °C ± 0.43 versus 1.38 °C ± 0.50, p < 0.001), but not for the other two fractions (p > 0.05 for both). The lower heat emission from this part of the airway (conductive airway) after exercise could mean that during hyperventilation heat emission is increased in this specific fraction. We can conclude that the changes of fEBT after physical exercise are not linear. They affect different fractions of the lungs in different ways, and the relationship between flow and volume on one side and the temperature of exhaled air on the other can vary significantly.

Dynamics of exhaled breath temperature after smoking a cigarette and its association with lung function changes predictive of COPD risk in smokers: a cross-sectional study.

Exhaled breath temperature (EBT) is a biomarker of inflammation and vascularity of the airways already shown to predict incident COPD. This cross-sectional study was aimed to assess the potential of EBT in identifying "healthy" smokers susceptible to cigarette smoke toxicity of the airways and to the risk of developing COPD by analysing the dynamics of EBT after smoking a cigarette and its associations with their demographics (age, smoking burden) and lung function. The study included 55 current smokers of both sexes, 29-62 years of age, with median smoking exposure of 15 (10-71.8) pack-years. EBT was measured at baseline and 5, 15, 30, 45, and 60 min after smoking a single cigarette. Lung function was measured with spirometry followed by a bronchodilator test. To compare changes in EBT between repeated measurements we used the analysis of variance and the area under the curve (EBTAUC) as a dependent variable. Multivariate regression analysis was used to look for associations with patient characteristics and lung function in particular. The average (±SD) baseline EBT was 33.42±1.50 °C. The highest significant increase to 33.84 (1.25) °C was recorded 5 min after the cigarette was smoked (p=0.003), and it took one hour for it to return to the baseline. EBTAUC showed significant repeatability (ICC=0.85, p<0.001) and was significantly associated with age, body mass index, number of cigarettes smoked a day, baseline EBT, and baseline FEF75 (R2=0.39, p<0.001 for the model). Our results suggest that EBT after smoking a single cigarette could be used as early risk predictor of changes associated with chronic cigarette smoke exposure.

Airway obstruction is associated with reduced variability in specific parts of the tidal breathing flow-volume curve in young children.

Impedance pneumography recordings during sleep at night show reduced variability in specific parts of the expiratory flow-volume curve in children with recurrent wheeze http://bit.ly/2Wkfap0.

Ragweed pollen and allergic symptoms in children: Results from a three-year longitudinal study.

Common ragweed is a highly allergenic invasive species in Europe, expected to become widespread under climate change. Allergy to ragweed manifests as eye, nasal and lung symptoms, and children may retain these throughout life. The dose-response relationship between symptoms and pollen concentrations is unclear. We undertook a longitudinal study, assessing the association between ragweed pollen concentration and allergic eye, nasal and lung symptoms in children living under a range of ragweed pollen concentrations in Croatia. Over three years, 85 children completed daily diaries, detailing allergic symptoms alongside daily location, activities and medication, resulting in 10,130 individual daily entries. The daily ragweed pollen concentration for the children's locations was obtained, alongside daily weather and air pollution. Parents completed a home/lifestyle/medical questionnaire. Generalised Additive Mixed Models established the relationship between pollen concentrations and symptoms, alongside other covariates. Eye symptoms were associated with mean daily pollen concentration over four days (day of symptoms plus 3 previous days); 61 grains/m3/day (95%CI: 45, 100) was the threshold at which 50% of children reported symptoms. Nasal symptoms were associated with mean daily pollen concentration over 12 days (day of symptoms plus 11 previous days); the threshold for 50% of children reporting symptoms was 40 grains/m3/day (95%CI: 24, 87). Lung symptoms showed a relationship with mean daily pollen concentration over 19 days (day of symptoms plus 18 previous days), with a threshold of 71 grains/m3/day (95%CI: 59, 88). Taking medication on the day of symptoms showed higher odds, suggesting responsive behaviour. Taking medication on the day prior to symptoms showed lower odds of reporting, indicating preventative behaviour. Different symptoms in children demonstrate varying dose-response relationships with ragweed pollen concentrations. Each symptom type responded to pollen exposure over different time periods. Using medication prior to symptoms can reduce symptom presence. These findings can be used to better manage paediatric ragweed allergy symptoms.

Inspiratory muscle strength affects anaerobic endurance in professional athletes.

To the best of our knowledge, little is known about the role of respiratory muscle strength and endurance on athlete performance in anaerobic conditions of maximal exertion. The aim of this cross-sectional study was therefore to examine the association between the strength/endurance of inspiratory muscles in a group of 70 healthy male professional athletes (team sports) and their ventilatory and metabolic parameters at the anaerobic threshold (second ventilatory threshold; VT2) and beyond it at maximum load during the cardiopulmonary exercise test (CPET) on a treadmill. Ventilatory parameters at VT2, at maximal effort, and their differences were tested for association with inspiratory muscle strength (PImax) and endurance (Tlim), measured as time to maintain inspiration at or above 80% of PImax. The difference in end-tidal oxygen tension (ΔPETO2) between VT2 and maximal effort was significantly associated with resting heart rate (HR) and systolic blood pressure (BP), PImax, and lean body mass (LBM) (r2=0.26, p=0.016; multivariate regression analysis). The difference in carbon dioxide output (ΔVCO2) was significantly associated with body mass index (BMI), resting HR, systolic BP, and PImax (r2=0.25, p=0.022; multivariate regression analysis). Our findings suggest that it is the inspiratory muscle strength and not endurance that affects the performance of professional athletes and that it should be tested and trained systematically.