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Background The prevalence of comorbidities and their relation to asthma control and treatment is a topic of increasing interest, however comprehensive studies are scarce. We aimed to determine the prevalence of the most common comorbidities in asthma in relation to patient characteristics (age, gender and body mass index [BMI]) and their association with asthma control in a large, specialist-managed representative patient population. Methods A secondary, exploratory analysis of the Asthma Reality (ARL), across-sectional, non-interventional real-life study was conducted. Basic patient characteristics, the prevalence of comorbidities and data on asthma control and risk factors had been collected and their interactions examined. Descriptive statistics and binomial regression were used to assess the distribution of the prevalence of comorbidities and propensity matching was applied to assess their effect on asthma control. Results Overall, 12,743 patients were enrolled in our study in 187 treatment centres covering all regions of Hungary. Most comorbidities showed significantly different distribution for all basic patient characteristics. Gender, age group, smoking status, BMI and the duration of asthma had a significant impact on asthma control. The frequency of uncontrolled asthma was higher in females (37.1%), in the age group of 46–65 years (39.6%), in severely obese patients (43.2%), in patients who had been diagnosed with asthma for more than 20 years (40.4%), and in active heavy smokers (55%), compared with respective groups in the same category. Based on the binomial regression with propensity score matching, concomitant chronic obstructive pulmonary disease (COPD) (odds ratio [OR] = 2.06, 95% confidence interval [CI] 1.80–2.36), ischaemic heart disease (OR = 1.86, 95% CI 1.64–2.10) and cerebrovascular events (OR = 1.85, 95% CI 1.47–2.32) had the strongest negative effect on asthma control, with the presence of all of these conditions increasing the risk of uncontrolled asthma. Conclusions This evaluation of comorbidity data of more than 12,000, adult asthmatic patients has provided a clearer picture of diseases that can frequently co-exist with asthma, and their influence on asthma control, assessed by the prevalence of symptoms. Our study suggests that most asthmatic patients have at least one comorbidity, and the presence of comorbidities may have a high impact on asthma control measures.

Összefoglaló. A dohányzás káros hatásainak vizsgálata hosszú ideje az orvostudomány egyik legintenzívebben kutatott területe. A nagy tudományos érdeklődésnek köszönhetően ma már meggyőző evidenciák állnak rendelkezésre a hagyományos cigaretta használatának számos negatív hatásáról. Ezzel ellentétben a sokkal később bevezetett helyettesítő termékek veszélyeiről lényegesen kevesebbet tudunk. E körbe tartozik a manapság egyre népszerűbb elektromos cigaretta is, amelyre egyre több, egészségügyi kockázatot felmérő munka fókuszál. Ugyanakkor a több évszázados múltra visszatekintő és a világ bizonyos helyein sokáig népszerű vízipipa érdekes esetnek számít, mivel használóinak száma a nyugati világban az utóbbi időben megugrott, de az emberre gyakorolt hatása számos ponton még vita tárgyát képezi. A jelen munka célja, hogy a hazai és a nemzetközi szakirodalom alapján feltérképezze a hagyományos cigaretta, az elektromos cigaretta és a vízipipa fontosabb egészségügyi hatásait, és rámutasson azokra a kapcsolódó területekre, ahol további kutatások szükségesek. A szakirodalmi áttekintés során a különböző publikációs adatbázisokban fellelhető tudományos cikkeket elemeztük. A megvizsgált szakirodalom alapján a tartós dohányzásnak bizonyítottan a szív-ér rendszert és a légzőrendszert károsító hatása van, de növekvő számú bizonyíték utal a neurológiai káros hatásokra és a gasztroenterológiai hatásokra is. Ugyanakkor az elektromos cigaretta és a vízipipa esetében a bizonyított akut hatások mellett a hosszú távú hatásokat illetően további intenzív kutatásokra van szükség. Az elektromos cigaretta és a vízipipa esetében a hosszú távú hatások kapcsán a meggyőző evidencia hiánya semmiképpen nem jelenti azt, hogy ezen termékeket kockázatmentesnek kellene tekinteni, sőt a pulmonológusoknak és a döntéshozóknak mindent meg kell tenniük annak érdekében, hogy valamennyi dohánytermék törvényi szabályozása azok használatának visszaszorítását célozza. A kérdés fontosságának a COVID–19-pandémia különös aktualitást ad. Orv Hetil. 2021; 162(3): 83–90. Summary. Revealing the health effects associated with smoking has been in the focus of intense research for decades. Due to these research efforts, there is a convincing evidence regarding the negative effects of conventional cigarettes. However, much less is known about the replacement products such as electronic cigarettes. Moreover, the effects of waterpipes are also not fully explored, in spite of their long history. The scope of the present work is to survey the open literature to map the knowledge related to the health effects of conventional cigarettes, e-cigarettes and waterpipes. The analysis of the related scientific literature was performed based on papers retrieved in large publication repositories. Based on the reviewed literature, long-term smoking has demonstrated adverse effects on the respiratory as well as the heart and circulatory systems. In addition, the correlation between cigarette smoking and some gastroenterological and neurological diseases is also increasingly evident. By the same token, though the acute effects of e-cigarette and waterpipe are well documented, the protracted effects are still to be explored. The lack of pertinent information regarding the late effects of e-cigarette and hookah does not imply that there is no health risk associated with their consumption. On the contrary, in addition to the regular antismoke measures, pulmonologists and policy makers should do everything to lower the consumption of these alternative products. Orv Hetil. 2021; 162(3): 83–90.

Background The study aimed to determine the prevalence and risk factors of allergic rhinitis and related comorbidities in school-age children in Budapest, capital of Hungary. Data and epidemiological studies on this disease are still limited. Methods A cross sectional study was conducted in 21 representative and randomly selected primary schools in 2019. International Study of Asthma and Allergies in Childhood-based questionnaires (n = 6869) inquiring about prevalence and related risk factors of allergic rhinitis were distributed to all parents. The data were characterised with standard descriptive statistics: frequencies (percentages) and means for categorical and quantitative data, respectively. Results 3836 of the questionnaires (1857 M/1979F) were completed. The prevalence of current allergic rhinitis was 29.3% (1043), physician-diagnosed allergic rhinitis was 9.7% (373), cumulative allergic rhinitis was 36.2% (1289) and current allergic rhinoconjunctivitis was 16.2% (577). The presence of physician diagnosed atopic disease–asthma (p Conclusions The prevalence of allergic rhinoconjunctivitis in 6–12-year-old children in Budapest is higher than reported for most of the surrounding European countries. While asthma (OR = 4.398) is the most significant comorbidity, environmental factors such as birds at home in the first year of life (OR = 2.394) and living in a weedy area (OR = 1.640) seem to be the most important factors associated with AR. Strategies for preventive measures should be implemented. Trial registration number: KUT-19/2019. The study was approved by the Ethics Committee at Heim Pál National Pediatric Institute

We aimed to evaluate the prevalence of asthma and its associating environmental factors within a 6–12-year-old population. A cross-sectional, questionnaire-based study was conducted in primary schools located in the capital of Hungary; 3836 eligible parent-reported questionnaires were evaluated. Besides the International Study of Asthma and Allergies in Childhood (ISAAC) phase three core questions for asthma, the survey also assessed various potential risk factors. We introduced the umbrella term cumulative asthma as the union of physician-diagnosed asthma and current wheezing to estimate the lifetime prevalence of asthma. Current wheezing and physician-diagnosed asthma showed a frequency of 9.5% and 6.3%, respectively. They contributed to a cumulative asthma prevalence of 12.6% among the sampled population, with a girl-boy percentage of 37.4% to 62.6%. Air-pollution and weedy areas were associated with greater risk for asthma, while a suburban residence showed lesser odds. Indoor smoking, visible mold, and keeping a dog were defined as risk factors for asthma, while the presence of plants in the bedroom and pet rodents were associated with lower odds ratios. The consumption of fast food, beverages containing additives and margarine were significantly higher in asthmatics, while we found frequent sport activity and cereal intake associated with lower odds ratios for asthma. In this urban environment, we identified an increased asthma prevalence compared to some previously published studies, but the cross-sectional design and the different methodology did not permit us to draw timeframe-dependent conclusions.

Introduction There are concerns about pulmonary function tests (PFT) being associated with aerosol generation and enhanced virus transmission. As a consequence, the number of PFTs was significantly reduced during the COVID-19 pandemic. However, there are no robust data supporting this fear. Objectives The aim of this work was to perform real-life measurement of aerosol concentration in a PFT laboratory to monitor the concentration of particles near the patient and to model the associated potential viral load. Methods Two optical particle counters (OPC) were used to sample the background concentration and the concentration of particles in the vicinity of the mouth of the patients in the whole-body plethysmography box. A statistical evaluation of the measured particle concentration time series was completed. The particle exhalation rate was assessed based on the measured particle concentration data by applying the near-field/far-field theory. The number of exhaled viruses by an infected patient during the test was assessed in comparison with the emission of viruses during quiet breathing and speaking. Results Twenty-five patients were involved in the study. Eighteen patients produced a significant increase of the aerosol concentration, which was 1910±593 particles/L. Submicron particles dominated the number size distribution of the generated particles, but large particles represented a higher volume fraction in the generated particles compared to the background. An average gene exhalation rate of 0.2/min was estimated from this data. This is one order of magnitude higher than the release rate of the same infected person during quiet breathing and of the same order of magnitude with the release rate during normal speaking. Conclusions Present results demonstrated that PFT is an aerosol generating procedure. Based on current results, the moderate increase of viral load does not underpin the stopping of such examinations.

Background Risk factors for poor asthma outcomes may have considerable influence on the control level and medical care of asthmatic patients. Our objective was to conduct a study that provides data on the level of symptom control and the frequency of specific risk factors for poor asthma outcomes on a large patient cohort. Methods A cross-sectional, non-interventional real-life study was conducted among asthmatic patients treated by respiratory specialists in Hungary. Asthma control and risk factor assessment were done according to Global Initiative for Asthma guideline (Box 2-2). In the data analysis, phase descriptive statistics, graphical outputs, and Fisher's exact tests were used. Results Of 12743 patients enrolled by 187 specialists, asthma was well controlled in 36.0%, partially controlled in 29.29%, and uncontrolled in 34.71% of the cases. The most common comorbidities were rhinitis/sinusitis (66.84%), cardiovascular diseases (43.81%), and gastroesophageal reflux disease (20.11%). The following risk factors had the strongest relationship with uncontrolled disease: incorrect inhaler technique causing side effects (odds ratio, OR 4.86, 3.51-6.8), previous severe exacerbation (OR 4.79, 4.02-5.72), high short-acting beta agonist (SABA) use (OR 4.46, 4.03-4.93), incorrect inhaler technique associated with an exacerbation (OR 3.91, 3.06-5.03), and persistently low forced expiratory volume in 1 s (FEV1, OR 3.14, 2.8-3.52). The most frequent risk factors were smoking (OR 1.47, 1.36-1.59) and obesity (OR 1.34, 1.24-1.45). Furthermore, high loss of control was associated with an initial low FEV1 (OR 2.21, 2.01-2.44), frequent oral corticosteroid (OCS) use (OR 1.83, 1.64-2.05), poor adherence to treatment (OR 2.51, 2.21-2.86), and allergen exposure (OR 1.63, 1.47-1.81). Conclusions This study indicated that the presence of risk factors for poor asthma outcomes listed by the Global Initiative for Asthma document significantly influenced actual control level in a real-world large patient cohort, with high SABA use, previous severe exacerbation, incorrect inhaler technique, persistently low FEV1, and poor adherence to treatment having the highest impact.

Introduction Drug emission from DPIs is dependent on the inspiratory flow parameters through them, which are not directly measured by standard spirometry. Their estimation based on native spirometric data could help in choosing the appropriate device and optimizing the drug deposition. Objectives The aim of this study was to survey patient preferences and to find correlations between breathing parameters of COPD patients through DPI devices and their baseline spirometric data, age, gender, disease severity and anthropometric characteristics. Another objective was to establish relationships between peak inspiratory flows (PIFdev) through Breezhaler®, Genuair® and Turbuhaler® inhalers and their determinants. Methods Breathing parameters of 49 patients with previously diagnosed COPD and currently using one of the above inhalers were recorded by normal spirometry and while inhaling through the selected DPIs. Statistical analysis of the measured data was completed. All specific data are provided as (mean ± standard deviation). Results More than 60% of the patients stated that their current device is the easiest to use. The means of the measured PIFdev values were 91.4 L/min, 77.1 L/min and 77.5 L/min for Breezhaler®, Genuair®, and Turbuhaler®, respectively. PIFdev values were significantly higher for males than for females, but differences upon age, BMI and disease severity group were not significant (at p = 0.05). Peak inspiratory flows through the inhalers (PIFdev) correlated best with their native spirometric counterparts (PIF) and linear PIFdev-PIF relationships could be determined (Breezhaler®: r = 0.60, p = 0.002, Genuair®: r = 0.55, p = 0.001, Turbuhaler®: r = 0.57, p = 0.002). Physical background of the deduced equations was also provided. Conclusions Present correlations may be used to assess the success of inhalation of COPD patients through the studied devices and to choose the appropriate device for each patient. As a consequence, the amount of the drug emitted by the device can be optimized, the deposition efficiency within the lungs increased and the related therapeutic effect improved.

Background A cross-sectional, questionnaire-based study was conducted in primary schools located in the capital of Hungary. We aimed to evaluate the prevalence of asthma and its risk factors within a 6-12-year-old population.Methods After meeting selection criteria, 3836 eligible parent-reported questionnaires were evaluated. The survey included the ISAAC phase three core questions for asthma and assessed the association with other atopic conditions and various environmental, lifestyle and nutritional risk factors.Results Cumulative asthma had a prevalence of 12.6% among the sampled population, with a girl-boy percentage of 37.4–62.6%. The proximity of any air-polluting factories, heavy-vehicle traffic and weedy area associated with greater risk for asthma while a suburban residence showed lesser odds (odds ratios were 1.3319, 1.2883, 1.3939 and 0.6390 respectively). Indoor smoking, visible mould, and keeping a dog were defined as risk factors for asthma (odds ratios: 1.6509, 2.1282, 1.4362), while the presence of a plant in the bedroom and pet rodents associated with lower odds ratios (0.7884, 0.7231 respectively). The consumption of fast food, beverages containing additives and margarine were significantly higher in asthmatics (odds ratios 1.7488, 1.2669, 1.3549), while we found frequent sport activity (0.6883) and cereal intake (0.5403) had favorable odds ratios for asthma.Conclusions Some of the obtained results have confirmed the outcomes of previous similar epidemiological studies, while in other cases, differences were found. These differences could have been a natural consequence of regional variability and other undiscovered factors; however, the correct evaluation of these controversial results require further investigation in the future. The current data can serve as a milestone for a prospective trial. Having the findings of this study, we can articulate recommendations for the public regarding the most common risk factors of asthma that should be avoided at home and in our surroundings and how to transform our daily habits for a prosperous future.

The new coronavirus disease 2019 (COVID-19) has been emerged as a rapidly spreading pandemic. The disease is thought to spread mainly from person-to-person through respiratory droplets produced when an infected person coughs, sneezes, or talks. The pathogen of COVID-19 is the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It infects the cells binding to the angiotensin-converting enzyme 2 receptor (ACE2) which is expressed by cells throughout the airways as targets for cellular entry. Although the majority of persons infected with SARS-CoV-2 experience symptoms of mild upper respiratory tract infection, in some people infections of the peripheral airways result in severe, potentially fatal pneumonia. However, the induction of COVID-19 pneumonia requires that SARS-CoV-2 reaches the peripheral airways. While huge efforts have been made to understand the spread of the disease as well as the pathogenesis following cellular entry, much less attention is paid how SARS-CoV-2 from the environment reach the receptors of the target cells. The aim of the present study is to characterize the deposition distribution of SARS-CoV-2 in the airways upon exposure to cough-generated aerosol. For this purpose, the Stochastic Lung Deposition Model has been applied. Aerosol size distribution and breathing parameters were taken from the literature supposing normal breathing through the nose. We found that the probability of direct infection of the peripheral airways due to inhalation of aerosol generated by a bystander cough is very low. As the number of pathogens deposited in the extrathoracic airways is ~10 times higher than in the peripheral airways, we concluded that in most cases COVID-19 pneumonia must be preceded by SARS-CoV-2 infection of the upper airways. Our results suggest that without the enhancement of viral load in the upper airways, COVID-19 would be much less dangerous..., Comment: 10 pages, 5 figures

The effect of breathing parameters on the airway deposition of the inhaled aerosols with known size was intensively studied in the literature. However, in the case of dry powder aerosol drugs both the quantity and quality of the particles emitted by the inhaler and inhaled by the patients is a complex function of the patient's breathing parameters, which in turn depend also on the disease severity and current status of the patient. The aim of this study was to evaluate the impact of breathing parameters, gender, age, symptoms and exacerbation history related disease severity (GOLD groups) of chronic obstructive pulmonary disease (COPD) patients on the lung dose of four different drugs emitted by three DPIs (dry powder inhalers). Breathing profiles of 47 COPD patients were recorded while they inhaled through Turbuhaler®, Breezhaler® and Genuair® inhalers. Patient specific emitted doses and particle size distributions were determined for Symbicort® Turbuhaler®, Onbrez® Breezhaler®, Seebri® Breezhaler® and Bretaris® Genuair® aerosol drugs. Airway deposition was quantified by a validated whole respiratory tract particle deposition model. Correlation analysis of the lung doses with breathing parameters through the devices and with standard spirometric parameters was performed. The effects of gender, age and degree of disease severity (GOLD groups) on the lung doses were also studied by statistical analysis. Mean values and distributions of the deposited lung doses proved to be both drug and device specific, yielding 24.2 (±7.8), 22.6 (±3.6), 34.2 (±4.8) and 23.9 (±5.4) % values for Symbicort®, Onbrez®, Seebri® and Bretaris®, respectively. Drugs with flow rate sensitive emitted dose and emitted particle size distribution exhibited higher intersubject variability of the lung doses. The degree of correlation of lung doses with breathing parameters through the devices was also drug specific. Correlation with flow rate was the strongest for Symbicort® Turbuhaler®. Longer breath-hold increased the lung dose of all the studied drugs. Correlations of lung dose with standard spirometric parameters was generally weaker than its correlation with the parameters measured when inhaling through the devices. Men had higher lung deposition than women, younger patients had higher deposition than older ones and patients with less severe disease higher doses than those with more severe COPD, but the differences were statistically significant only upon gender and only in case of Symbicort® and Seebri®. Patients with better inhalation parameters are likely to have higher lung deposition when inhaling a drug with emitted dose and particle size distribution sensitive to the inhalation flow rate. At the same time, patients with lower lung capacity show better deposition results when inhaling from inhalers emitting a more constant amount of drug and particles with more stable aerodynamic characteristics. A more powerful inhalation significantly increases the lung dose for the drug emitted by Turbuhaler®, while long breath-hold is likely to yield significantly higher deposition for drugs emitted by Breezhaler® and Genuair®. Lung doses of two different drugs dispensed in the same inhaler can be significantly different.

Lack of coordination between the beginning of the inhalation and device triggering is one of the most frequent errors reported in connection with the use of pMDI devices. Earlier results suggested a significant loss in lung deposition as a consequence of late actuation. However, most of our knowledge on the effect of poor synchronization is based on earlier works on CFC devices emitting large particles with high initial velocities. The aim of this study was to apply numerical techniques to analyse the effect of late device actuation on the lung dose of a HFA pMDI drug emitting high fraction of extrafine particles used in current asthma and COPD therapy. A computational fluid and particle dynamics model was combined with stochastic whole lung model to quantify the amount of drug depositing in the extrathoracic airways and in the lungs. High speed camera measurements were also performed to characterize the emitted spray plume. Our results have shown that for the studied pMDI drug late actuation leads to reasonable loss in terms of lung dose, unless it happens in the second half of the inhalation period. Device actuation at the middle of the inhalation caused less than 25% lung dose reduction relative to the value characterizing perfect coordination, if the inhalation time was between 2 and 5 s and inhalation flow rate between 30 and 150 L/min. This dose loss is lower than the previously known values of CFC devices and further support the practice of triggering the device shortly after the beginning of the inhalation instead of forcing a perfect synchronization and risking mishandling and poor drug deposition.

Comorbidities associated with chronic obstructive pulmonary disease (COPD) affect quality of life and increase mortality. Asthma–COPD overlap (ACO) may express a different profile of comorbidities compared to COPD alone. It is unclear how recent changes in GOLD recommendations affect the profile of comorbidities in COPD and ACO. Eight hundred and thirty-four patients with COPD were recruited from 67 Hungarian secondary care outpatient clinics, 469 of them had ACO. Comorbidities were defined by respiratory specialists based on medical history, patient report, and medications. COPD grades were defined according to the old 2016 and the new 2017 GOLD document. Comorbidities were compared along COPD ABCD groups determined by the old and new GOLD. 66 and 72% of the COPD patients in groups C and D (GOLD 2016) were recategorized to groups A and B (GOLD 2017), respectively. There was no difference in the prevalence of disorders along the 2016 GOLD categories except for osteoporosis in ACO (p = 0.01). When the patients were categorized according to the 2017 GOLD criteria, the prevalence of osteoporosis (p = 0.01) was different among the four groups in all COPD patients. Subgroup analysis of non-ACO COPD patients revealed inter-group differences for cardiac arrhythmia (p

Purpose. The health-related quality of life (HRQL) in chronic obstructive pulmonary disease (COPD) is worsened by frequent exacerbations, and it can be affected by the concomitant presence of bronchial asthma (asthma-COPD overlap (ACO)). The impacts of clinical factors associated with HRQL have not been compared in patients with COPD and ACO experiencing exacerbations. Patients and Methods. Patients with COPD (N =705) and ACO (N =148) belonging to C and D groups according to GOLD 2017 were recruited in stable condition. Demographic and clinical data were collected, spirometry was performed, and patients rated the intensity of respiratory symptoms during the previous week. The COPD Assessment Test (CAT) and the EQ-5D 3 level version (dimensions and visual analogue scale (VAS)) were used to assess disease-specific and generic HRQL, respectively. Fisher’s exact test, χ2 test, ANOVA, and Pearson correlation were used for analysis (mean±SD). Multiple linear regression was applied to identify variables related to CAT and EQ-5D VAS scores. Results. The CAT and EQ-5D VAS scores showed similarly low HRQL in COPD and ACO (20.7±6.7 vs. 21.1±6.3 (p=0.52) and 56.2±17.8 vs. 53.7±18.2 (p=0.11)). There was a weak correlation between CAT and EQ-5D VAS scores (COPD: r=−0.345, p<0.001; ACO: r=−0.245, p=0.003). More patients with COPD had problems related to anxiety/depression in EQ-5D (63.7% vs. 55.4%, p=0.06). Pack-years exerted a negative effect on HRQL measures both in ACO and COPD. Low HRQL in COPD was associated with female gender, dyspnea, cough, gastroesophageal reflux disease, and arrhythmia, while in ACO, it was related to arrhythmia, hypertension, and cough, but less to dyspnea. Conclusions. Patients with COPD and ACO experiencing exacerbations have low quality of life, which is influenced by smoking history, symptoms, and comorbidities. These findings have important implications for the development of therapeutic strategies to improve the health status of patients with these conditions.

Medical aerosols are key elements of current chronic obstructive pulmonary disease (COPD) therapy. Therapeutic effects are conditioned by the delivery of the right amount of medication to the right place within the airways, that is, to the drug receptors. Deposition of the inhaled drugs is sensitive to the breathing pattern of the patients which is also connected with the patient&rsquo, s disease severity. The objective of this work was to measure the realistic inhalation profiles of mild, moderate, and severe COPD patients, simulate the deposition patterns of Symbicort&reg, Turbuhaler&reg, dry powder drug and compare them to similar patterns of healthy control subjects. For this purpose, a stochastic airway deposition model has been applied. Our results revealed that the amount of drug depositing within the lungs correlated with the degree of disease severity. While drug deposition fraction in the lungs of mild COPD patients compared with that of healthy subjects (28% versus 31%), lung deposition fraction characteristic of severe COPD patients was lower by a factor of almost two (about 17%). Deposition fraction of moderate COPD patients was in-between (23%). This implies that for the same inhaler dosage severe COPD patients receive a significantly lower lung dose, although, they would need more.

One of the most widespread dry powder fixed combinations used in asthma and chronic obstructive pulmonary disease (COPD) management is Symbicort(®) Turbuhaler(®). The aim of this study was to simulate the deposition distribution of both components of this drug within the airways based on realistic airflow measurements. Breathing parameters of 25 healthy adults (11 females and 14 males) were acquired while inhaling through Turbuhaler(®). Individual specific emitted doses and particle size distributions of Symbicort(®) Turbuhaler(®) were determined. A self-developed particle deposition model was adapted and validated to simulate the deposition of budesonide (inhaled corticosteroid; ICS) and formoterol (long acting β2 agonist; LABA) in the upper airways and lungs of the healthy volunteers. Based on current simulations the emitted doses varied between 50.4% and 92.5% of the metered dose for the ICS, and between 38% and 96.1% in case of LABA component depending on the individual inhalation flow rate. This variability induced a notable inter-individual spread of the deposited lung doses (mean: 33.6%, range: 20.4%-48.8% for budesonide and mean: 29.8%, range: 16.4%-42.9% for formoterol). Significant inter-gender differences were also observed. Average lung dose of budesonide was 29.2% of the metered dose for females and 37% for males, while formoterol deposited with 26.4% efficiency for females and 32.5% for males. Present results also highlighted the importance of breath-holding after inhalation of the drug. About a half of the total lung deposition occurred during breath-hold at 9.6s average breath-hold time. Calculated depositions confirmed appropriate lung deposition of Symbicort(®) Turbuhaler(®) for both genders, however more effort for optimal inhalation technique is advised for persons with low vital capacity. This study demonstrated the possibility of personalized prediction of airway deposition of aerosol drugs by numerical simulations. The methodology developed in this study will be applicable also to other marketed drugs in the future.

Asthma is a serious global health problem with rising prevalence and treatment costs. Due to the growing number of different types of inhalation devices and aerosol drugs, physicians often face difficulties in choosing the right medication for their patients. The main objectives of this study are (i) to elucidate the possibility and the advantages of the application of numerical modeling techniques in aerosol drug and device selection, and (ii) to demonstrate the possibility of the optimization of inhalation modes in asthma therapy with a numerical lung model by simulating patient-specific drug deposition distributions. In this study we measured inhalation parameter values of 25 healthy adult volunteers when using Foster(®) NEXThaler(®) and Seretide(®) Diskus(®). Relationships between emitted doses and patient-specific inhalation flow rates were established. Furthermore, individualized emitted particle size distributions were determined applying size distributions at measured flow rates. Based on the measured breathing parameter values, we calculated patient-specific drug deposition distributions for the active components (steroid and bronchodilator) of both drugs by the help of a validated aerosol lung deposition model adapted to therapeutic aerosols. Deposited dose fractions and deposition densities have been computed in the entire respiratory tract, in distinct anatomical regions of the airways and at the level of airway generations. We found that Foster(®) NEXThaler(®) deposits more efficiently in the lungs (average deposited steroid dose: 42.32±5.76% of the nominal emitted dose) than Seretide(®) Diskus(®) (average deposited steroid dose: 24.33±2.83% of the nominal emitted dose), but the variance of the deposition values of different individuals in the lung is significant. In addition, there are differences in the required minimal flow rates, therefore at certain patients Seretide(®) Diskus(®) or pMDIs could be a better choice. Our results show that validated computer deposition models could be useful tools in providing valuable deposition data and assisting health professionals in the personalized drug selection and delivery optimization. Patient-specific modeling could open a new horizon in the treatment of asthma towards a more effective personalized medicine in the future.

Introduction: The objective of this study was to investigate with the help of a computerized simulation model whether the treatment of an acute asthma attack can be individualized based on the severity of the attack and the characteristics of the patient. Material and Method: A stochastic lung model was used to simulate the deposition of 1 nm - 10 μm particles during a mild and a moderate asthma attack. Breathing parameters were varied to maximize deposition, and simulation results were compared with those obtained in the case of a severe asthma attack. In order to investigate the effect of height on the deposition of inhaled particles, another series of simulations was carried out with identical breathing parameters, comparing patient heights of 155 cm, 175 cm and 195 cm. Results: The optimization process yielded an increase in the maximum deposition values of around 6-7% for each type of investigated asthma attack, and the difference between attacks of different degree of severity was around 5% for both the initial and the optimized values, a higher degree of obstruction increasing the amount of deposited particles. Conclusions: Our results suggest that the individualization of asthma attack treatment cannot be based on particles of different size, as the highest deposited fraction in all three types of attacks can be obtained using 0.01 μm particles. The use of a specific set of breathing parameters yields a difference between a mild and a moderate, as well as a moderate and a severe asthma attack of around 5%.

In our study, we wanted to assess the workload under which health professionals work with asthmatic and COPD patients, the average time spent on investigation, patient care, patient education and on checking their previously acquired knowledge. We also wanted to know who educates these patients to the proper use of inhalation devices and how often they check their usage. We have conducted personal interviews and online surveys among health professionals. We made distinguished time spent on “freshly” diagnosed patients, routine control examinations and previously diagnosed patients. Participants: asthma nurses from the pulmonary care network, hospital departments, specialized practices and pulmonary care units; pulmonologists; specialists from internal medicine departments and emergency health care centres and GPs (general practitioners). Our results show that in every group of healthcare professionals involved in the treatment of these patients, the number of daily meetings between healthcare professionals and patients is remarkably high (an average of 30 patients a day), and there is not enough time for patient education. Checking the proper usage of the device is often skipped and no appropriate educational materials are available. Patients are not likely to have sufficient knowledge of their disease or the appropriate usage of their inhalation devices. Reorganization of the Hungarian COPD and asthmatic patient care system is needed as soon as possible to provide effective patient education and patient care.

The number of patients with obstructive airway disease has been increasing worldwide. The delivery of aerosol drugs through the respiratory system has become a central element in the management of asthma and chronic obstructive pulmonary disease (COPD). The aim of this study was to validate and apply a stochastic whole respiratory tract deposition model in order to characterize airway deposition distribution of two different marketed drugs delivered in form of dry powders (Seretide® Diskus® and Symbicort® Turbuhaler®), and to analyze the possibility of computerized drug delivery optimization in the future. Spirometry measurements on 17 adult volunteers have been performed. Relationships between breathing parameters measured during diagnostic spirometry and those characterising breathing during drug administration through Diskus® and Turbuhaler® inhalers have been derived. The doses deposited in different anatomical regions of the respiratory tract and airway generation number specific deposited doses have been computed for the participating individuals based on both mass median aerodynamic diameter (MMAD) and detailed size distribution of the two drugs. Although regional deposited doses were not very different in the two cases, airway generation number specific deposition distributions were sensitive to this input parameter, indicating the need for the whole size distribution when modelling airway deposition of aerosol drugs. Significant intersubject variability in terms of oropharyngeal, bronchial and acinar deposited doses have been found. The results highlight the necessity for and open the possibility of simulation assisted customized drug selection in the future.

The breath-actuated mechanism (BAM) is a mechanical unit included in NEXThaler® with the role of delaying the emission of the drug until the inhalation flow rate of the patient is sufficiently high to detach the drug particles from their carriers. The main objective of this work was to analyse the effect of the presence of BAM on the size distribution of the emitted drug and its airway deposition efficiency and distribution. Study of the hygroscopic growth of the emitted drug particles and its effect on the deposition was another goal of this study. Size distributions of Foster® NEXThaler® drug particles emitted by dry powder inhalers with and without BAM have been measured by a Next Generation Impactor. Three characteristic inhalation profiles of asthmatic patients (low, moderate and high flow rates) were used for both experimental and modelling purposes. Particle hygroscopic growth was determined by a new method, where experimental measurements are combined with simulations. Upper airway and lung deposition fractions were computed assuming 5s and 10s breath-hold times. By the inclusion of BAM the fine particle fraction of the steroid component increased from 24 to 30% to 47-51%, while that of bronchodilator from 25-34% to 52-55%. The predicted upper airway steroid and bronchodilator doses decreased from about 60% to 35-40% due to BAM. At the same time, predicted lung doses increased from about 20%-35% (steroid) and from 22% to 38% (bronchodilator) for the moderate flow profile and from about 25% to 40% (steroid) and from 29% to 47% (bronchodilator) for the high inhalation flow profile. Although BDP and FF upper airway doses decreased by a factor of about two when BAM was present, lung doses of both components were about the same in the BAM and no-BAM configurations at the weakest flow profile. However, lung dose increased by 2-3% even for this profile when hygroscopic growth was taken into account. In conclusion, the NEXThaler® BAM mechanism is a unique feature enabling high emitted fine particle fraction and enhanced drug delivery to the lungs.

Introduction: The breath-actuated mechanism (BAM) is a mechanical unit included in NEXThaler® with the role of delaying the emission of the drug until the inhalation flow rate of the patient is sufficiently high to detach the drug particles from their carriers. Objective: The main objective of this study was to analyse the effect of the presence of BAM on the size distribution of the emitted drug and its airway deposition efficiency and distribution. Methods: Size distributions of Foster® NEXThaler® drug particles emitted by dry powder inhalers (DPI) with and without BAM have been measured by a Next Generation Impactor (NGI). p50 inhalation profile of asthmatic patients was used for both experimental and modelling purposes. Upper airway and lung deposition fractions were computed assuming 10 s breath-hold time. Results: The number of emitted fine and extrafine particles increased by the inclusion of BAM (Figure 1). Fine particle fraction (FPF) of the steroid component increased from 26.7% to 49.3%. Upper airway dose expressed as a percent of the nominal emitted dose decreased from 74% to 51%, while lung dose increased from 25.5% to 40% due to BAM. Figure 1. Cumulative size distribution Conclusion: The Chiesi NEXThaler® BAM mechanism is a unique feature enabling enhanced drug delivery to the lungs.

Aerosol drugs are effectively used to treat chronic respiratory diseases. The efficiency of the therapy depends also on the amount and distribution of drug deposited within the airways. The objective of this study is to apply numerical techniques to analyse the effect of the duration of breath-hold after the inhalation of six different commercialized dry powder drugs on their lung deposition. For this purpose a computational airway deposition model has been adapted and validated to the special case of therapeutic aerosols. Our results show that lung dose of the studied drugs can be enhanced by 11.3%-26.5% with a 5s breath-hold and by 20.7%-53% with a 25s breath-hold compared to the no-breath-hold case. Although this later duration may not be achieved by COPD patients, present results clearly show the importance of holding the breath as long as possible. Current computations also revealed that there is a strong positive correlation between the enhancement of lung dose as a result of breath-hold and the amount of fine particles in the drugs. Present tendencies aiming at producing drug particles of smaller and smaller sizes will lead to the further enhancement of the importance of producing a sufficiently long breath-hold time after the drug inhalation. In addition, higher lung deposition will be possible by the more correct use of inhalation devices, more precise and detailed patient information materials and personalized drug choice and therapy.

Although pollen is one of the most widespread agents that can cause allergy, its airway transport and deposition is far from being fully explored. The objective of this study was to characterize the airway deposition of pollens and to contribute to the debate related to the increasing number of asthma attacks registered after thunderstorms. For the quantification of the deposition of inhaled pollens in the airways computer simulations were performed. Our results demonstrated that smaller and fragmented pollens may penetrate into the thoracic airways and deposit there, supporting the theory that fragmented pollen particles are responsible for the increasing incidence of asthma attacks following thunderstorms. Pollen deposition results also suggest that children are the most exposed to the allergic effects of pollens. Finally, pollens between 0.5 and 20 μm deposit more efficiently in the lung of asthmatics than in the healthy lung, especially in the bronchial region.

COPD is a spreading respiratory disease claiming more and more deaths. The aim of this study was to develop a method, which enables the computerized recognition of COPD in the course of pulmonary screening. At pulmonary screening only a PA radiograph is recorded, but some additional data can be measured automatically. Parameters indicating COPD have been derived from the chest radiograph using complex image processing algorithms. Neural network based classifiers were applied to select the patients with the suspicion of COPD. Results show that although diagnosis is not possible, the majority of COPD cases can be sorted out.

Background Life-long regular use of drugs is necessary in chronic diseases like asthma and COPD. There are several methods to improve adherence including patient information and education; however, their effectiveness on the basis of practical experience is often lower than originally planned and expected. Our objective is to develop a patient information material based on the recommendations of patients and their treating healthcare professionals to fulfill their needs. Methods A survey was conducted among pulmonologists (N = 262), asthma nurses (N = 102), general practitioners (N = 321) and patients with obstructive pulmonary disease (N = 978) using on line questionnaires. Results All surveyed population would prefer to use 1 to 5 pages long, A5 format patient information material based on topics considered important by patients that is appropriately segmented with pictures as well as supplementary information cards adapted to the life situation of patients and the severity of their disease. Questioned population (whose mean age was 57.2) preferred highly informative printed material. Conclusions For more effective information and improvement of adherence we recommend newly structured patient information sheets and information cards with content discussed with the targeted patients and their healthcare professionals. Customized, patient-centered information materials could improve the efficiency of patient education and make the follow-up of the various therapeutic plans easier for patients. Electronic supplementary material The online version of this article (doi:10.1186/s40248-017-0087-2) contains supplementary material, which is available to authorized users.