Comparative study of the inhalation parameters of COPD patients through NEXThaler® and Ellipta® dry powder inhalers.

The deposition of dry powder aerosol drugs depends on the inhalation parameters of the patients through the inhaler. These data are not directly measured in clinical practice. Their prediction based on the routinely measured spirometric data could help in choosing the appropriate device and optimizing the therapy. The aim of this study was to perform inhalation experiments to find correlations between inhalation parameters of COPD patients through two DPI devices and their native spirometric data, gender, age and disease severity. Another goal was to establish relationships between peak inspiratory flows through NEXThaler® and Ellipta® inhalers and their statistical determinants. Breathing parameters of 113 COPD patients were measured by normal spirometry and while inhaling through the two DPIs. Statistical analysis of the measured data was performed. The average values of peak inspiratory flow through the devices (PIFdev) were 68.4 L/min and 78.0 L/min for NEXThaler® and Ellipta®, respectively. PIFdev values were significantly higher for males than for females, but differences upon age, BMI and disease severity group were not significant. PIFdev values correlated best with their native spirometric counterparts (PIF) and linear relationships between them were revealed. Current results may be used in the future to predict the success of inhalation of COPD patients through DPI devices, which may help in the inhaler choice. By choosing the appropriate device-drug pair for each patient the lung dose can be increased and the efficiency of the therapy improved. Further results of the clinical study will be the subject of a next publication.

Risk of exacerbation and mortality in asthma: a 10-year retrospective financial database analysis of the Hungarian Health Insurance Fund.

INTRODUCTION: Asthma is the most prevalent obstructive pulmonary disease, with drastically improved treatment options over the past decades. However, there is still a proportion of patients with suboptimal level of asthma control, leading to multiple hospitalisation due to severe acute exacerbation (SAE) and earlier death. In our study, we aimed to assess the risk of SAEs and mortality in patients who suffered an SAE. METHODS: The database of the National Health Insurance Fund was used to retrospectively analyse the data of all asthmatic patients who had been hospitalised for an SAE between 2009 and 2019. We used a competing risk model to analyse the effect of each exacerbation on the risk of further SAEs with age, sex, Charlson index and the number of severe and moderate exacerbations included as covariates. RESULT: Altogether, 9257 asthmatic patients suffered at least one exacerbation leading to hospitalisation during the study time. The majority (75.8%) were women, and the average age was 58.24 years. Most patients had at least one comorbidity. 3492 patients suffered at least one further exacerbation and 1193 patients died of any cause. In the competing risk model, each SAE increased the risk of further exacerbations (HR=2.078-7.026; p<0.0001 for each case) but not death. The risk of SAEs was also increased by age (HR=1.008) female sex (HR=1.102) and with the number of days of the first SAE (HR=1.007). CONCLUSIONS: Even though asthma is generally a well-manageable disease, there still are many patients who suffer SAEs that significantly increase the risk of further similar SAEs.

The effect of lung emptying before the inhalation of aerosol drugs on drug deposition in the respiratory system.

The amount of drug depositing in the airways depends, among others, on the inhalation manoeuvre and breathing parameters. The objective of this study was to quantify the effect of lung emptying before the inhalation of drugs on the lung doses. Thirty healthy adults were recruited. Their breathing profiles were recorded while inhaling through six different emptied DPI devices without breathe-out and after comfortable or forced exhalation. The corresponding emitted doses and aerosol size distributions were derived from the literature. The Stochastic Lung Model was used to estimate the deposited doses. In general, forceful exhalation caused increased flow rate and inhaled air volume. Increased flow rate led to the increase of the average lung dose for drugs with positive lung dose-flow rate correlation (e.g. Symbicort®: relative increase of 6.7%, Bufomix®: relative increase of 9.2%). For drugs with negative correlation of lung dose with flow rate (all the studied drugs except the above two) lung emptying caused increased (Foster® by 2.7%), almost unchanged (Seebri®, Relvar®, Bretaris®) and also decreased (Onbrez® by 6.6%) average lung dose. It is worth noting that there were significant inter-individual differences, and lung dose of each drug could be increased by a number of subjects. In conclusion, the change of lung dose depends on the degree of lung emptying, but it is also inhaler and drug specific. Forceful exhalation can help in increasing the lung dose only if the above specificities are taken into account.

First booster dose uptake of COVID-19 vaccine and disease-related factors in chronic obstructive pulmonary disease-a cross-sectional survey in Hungary.

BACKGROUND: In chronic obstructive pulmonary disease (COPD), uptake of the coronavirus disease 2019 (COVID-19) booster vaccine is important, as they are more likely to develop serious complications. Our aim was to investigate the uptake rate of first booster vaccination against COVID-19 among COPD patients and to identify other related factors of vaccine uptake. METHODS: We conducted a multicenter survey of COPD patients in Hungary by region: eastern, western and central ones from 15 November 2021. Respiratory function test results, anthropometric data and vaccination status were recorded for 1,510 randomly selected patients over 35 years of age. Multiple logistic regression analysis was used to determine factors associated with uptake of COVID-19 first booster dose vaccines. RESULTS: The average age was 67 [61-72] years, for men it was: 67 [62-73] and 66 [60-72] years for women, with a sample of 47.95% men and 52.05% women. The uptake rate of the COVID-19 first booster vaccine during the study period was 62.45%. Comparing patients who received the 3rd vaccine with those who did not receive the 3rd vaccine, the difference was significant in quality of life: COPD Assessment Test (CAT): 16 [11-21] vs. 14 [10-19], P<0.001, modified Medical Research Council (mMRC) dyspnea scale: 2 [2-2] vs. 2 [1-2], P=0.01 and in the number of moderate exacerbations: 1 [0-1] vs. 0 [0-1], P=0.04. In addition, who did not take the third vaccination significantly more people were hospitalized for acute severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (16 vs. 0, P<0.001) and almost the same proportion (n=14) required pulmonary outpatient rehabilitation for post-COVID symptoms. The factors that were most associated with higher COVID-19 vaccine first booster dose uptake were older age [odds ratio (OR): 1.06; 95% confidence interval (CI): 1.04-1.08], male gender (OR: 0.74; 95% CI: 0.57-0.96), absence of previous COVID-19 infection (OR: 0.34; 95% CI: 0.23-0.51). CONCLUSIONS: The uptake rate of the COVID-19 booster vaccine among COPD patients in Hungary is lower than the target, and is associated with disease-related factors, and age, sex, previous COVID infection. The global COVID-19 vaccination target is 70% and 100% for elderly, vulnerable patients. Highlighting the importance of taking booster vaccine(s) should be a priority for health workers.

The effect of exhalation before the inhalation of dry powder aerosol drugs on the breathing parameters, emitted doses and aerosol size distributions.

Airway deposition of aerosol drugs is highly dependent on the breathing manoeuvre of the patients. Though incorrect exhalation before the inhalation of the drug is one of the most common mistakes, its effect on the rest of the manoeuvre and on the airway deposition distribution of aerosol drugs is not explored in the open literature. The aim of the present work was to conduct inhalation experiments using six dry powder inhalers in order to quantify the effect of the degree of lung emptying on the inhalation time, inhaled volume and peak inhalation flow. Another goal of the research was to determine the effect of the exhalation on the aerodynamic properties of the drugs emitted by the same inhalers. According to the measurements, deep exhalation before drug inhalation increased the volume of the inhaled air and the average and maximum values of the inhalation flow rate, but the extent of the increase was patient and inhaler specific. For different inhalers, the mean value of the relative increase in peak inhalation flow due to forceful exhalation was between 15.3 and 38.4% (min: Easyhaler®, max: Breezhaler®), compared to the case of normal (tidal) exhalation before the drug inhalation. The relative increase in the inhaled volume was between 36.4 and 57.1% (min: NEXThaler®, max: Turbuhaler®). By the same token, forceful exhalation resulted in higher emitted doses and smaller emitted particles, depending on the individual breathing ability of the patient, the inhalation device and the drug metered in it. The relative increase in the emitted dose varied between 0.2 and 8.0% (min: Foster® NEXThaler®, max: Bufomix® Easyhaler®), while the relative enhancement of fine particle dose ranged between 1.9 and 30.8% (min: Foster® NEXThaler®, max: Symbicort® Turbuhaler®), depending on the inhaler. All these effects and parameter values point toward higher airway doses due to forceful exhalation before the inhalation of the drug. At the same time, the present findings highlight the necessity of proper patient education on the importance of lung emptying, but also the importance of patient-specific inhaler-drug pair choice in the future.

COVID-19 vaccination coverage in patients with chronic obstructive pulmonary disease - A cross-sectional study in Hungary.

INTRODUCTION: Coronavirus infection is a particular risk for patients with chronic obstructive pulmonary disease (COPD), because they are much more likely to become severely ill due to oxygen supply problems. Primary prevention, including COVID-19 vaccination is of paramount importance in this disease group. The aim of our study was to assess COVID-19 vaccination coverage in COPD patients during the first vaccination campaign of the COVID-19 pandemic. METHODS: A cross-sectional observational study (CHANCE) has been conducted in COPD patients in the eastern, western and central regions of Hungary from 15th November 2021. The anthropometric, respiratory function test results and vaccination status of 1,511 randomly selected patients were recorded who were aged 35 years and older. RESULTS: The median age was 67 (61-72) years, for men: 67 (62-73) and for women: 66 (60-72) years, with 47.98 % men and 52.02 % women in our sample. The prevalence of vaccination coverage for the first COVID-19 vaccine dose was 88.62 %, whereas 86.57 % of the patients received the second vaccine dose. When unvaccinated (n = 172) and double vaccinated (n = 1308) patients were compared, the difference was significant both in quality of life (CAT: 17 (12-23) vs 14 (10-19); p < 0.001) and severity of dyspnea (mMRC: 2 (2-2) vs 2 (1-2); p = 0.048). The COVID-19 infection rate between double vaccinated and unvaccinated patients was 1.61 % vs 22.67 %; p < 0.001 six months after vaccination. The difference between unvaccinated and vaccinated patients was significant (8.14 % vs 0.08 %; p < 0.001) among those with acute COVID-19 infection hospitalized. In terms of post-COVID symptoms, single or double vaccinated patients had significantly fewer outpatient hospital admissions than unvaccinated patients (7.56 vs 0 %; p < 0.001). CONCLUSION: The COVID-19 vaccination coverage was satisfactory in our sample. The uptake of COVID-19 vaccines by patients with COPD is of utmost importance because they are much more likely to develop severe complications.

Do we really target the receptors? Deposition and co-deposition of ICS-LABA fixed combination drugs.

Fixed dose combinations of aerosolized bronchodilators and steroids are routinely used in current asthma and COPD management. As spatial distribution of their receptors within the human airways is different, it is a challenging task to deliver the right drug component to the right receptor. The aim of this work was to apply numerical methods to analyse the airway deposition distribution of two inhalation corticosteroid (ICS) - long-acting beta-agonist (LABA) combination drugs in comparison with the distribution of the corresponding receptors. Our results revealed that different combination drugs exhibit different co-deposition patterns depending on the aerodynamic properties of their components. While ICS and LABA components of Symbicort® Turbuhaler® had similar deposition efficiencies in the same airway generation throughout the whole respiratory tract, the steroid component of Relvar® Ellipta® had up to 25% higher deposition than its bronchodilator component in the large bronchi and up to 40% lower deposition in the deeper airways. Present results highlight the need for extensive research to elucidate whether each drug component should deposit according to its receptor distribution or similar deposition distribution patterns of the components should be attained to benefit from the synergistic effects documented in the open literature. Once this aspect clarified, the next step will be to tailor the aerodynamic properties of each component of combination drugs to yield the desired deposition distribution in the lungs.

Prevalence of Asthma and Its Associating Environmental Factors among 6-12-Year-Old Schoolchildren in a Metropolitan Environment-A Cross-Sectional, Questionnaire-Based Study.

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.

Epidemiology of comorbidities and their association with asthma control.

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.

Health effects of cigarettes, electronic cigarettes and waterpipes / A cigaretta, az elektromos cigaretta és a vízipipa egészségre gyakorolt hatása.

Összefoglaló. A dohányzás káros hatásainak vizsgálata hosszú ideje az orvostudomány egyik legintenzívebben kutatott területe. A nagy tudományos érdeklodésnek köszönhetoen ma már meggyozo evidenciák állnak rendelkezésre a hagyományos cigaretta használatának számos negatív hatásáról. Ezzel ellentétben a sokkal késobb bevezetett helyettesíto termékek veszélyeirol lényegesen kevesebbet tudunk. E körbe tartozik a manapság egyre népszerubb elektromos cigaretta is, amelyre egyre több, egészségügyi kockázatot felméro munka fókuszál. Ugyanakkor a több évszázados múltra visszatekinto és a világ bizonyos helyein sokáig népszeru vízipipa érdekes esetnek számít, mivel használóinak száma a nyugati világban az utóbbi idoben 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 különbözo publikációs adatbázisokban fellelheto tudományos cikkeket elemeztük. A megvizsgált szakirodalom alapján a tartós dohányzásnak bizonyítottan a szív-ér rendszert és a légzorendszert károsító hatása van, de növekvo 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 illetoen további intenzív kutatásokra van szükség. Az elektromos cigaretta és a vízipipa esetében a hosszú távú hatások kapcsán a meggyozo evidencia hiánya semmiképpen nem jelenti azt, hogy ezen termékeket kockázatmentesnek kellene tekinteni, sot 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.

Impact of Clinical Factors on Generic and Disease-Specific Quality of Life in COPD and Asthma-COPD Overlap with Exacerbations.

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, χ 2 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.

Numerical simulation of the effect of inhalation parameters, gender, age and disease severity on the lung deposition of dry powder aerosol drugs emitted by Turbuhaler®, Breezhaler® and Genuair® in COPD patients.

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.

Prevalence and impact of risk factors for poor asthma outcomes in a large, specialist-managed patient cohort: a real-life study.

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.

Changes in the Burden of Comorbidities in Patients with COPD and Asthma-COPD Overlap According to the GOLD 2017 Recommendations.

PURPOSE: 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. METHODS: 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. RESULTS: 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 < 0.01). No alteration was seen in the prevalence of coronary artery disease, hypertension, diabetes, or the total number of comorbidities. CONCLUSION: A significant number of patients are recategorized according to the GOLD 2017 criteria. This change only marginally affects the profile of comorbidities; still this needs to be considered when assessing the patients in daily practice.

Effect of delayed pMDI actuation on the lung deposition of a fixed-dose combination aerosol drug.

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.

Significance of breath-hold time in dry powder aerosol drug therapy of COPD patients.

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.

Characteristics of an optimized patient information material for elderly patients with obstructive pulmonary diseases based on patients' and experts' assessment.

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.

Numerical simulation of emitted particle characteristics and airway deposition distribution of Symbicort(®) Turbuhaler(®) dry powder fixed combination aerosol drug.

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 ß2 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.

Computer modeling of airway deposition distribution of Foster(®) NEXThaler(®) and Seretide(®) Diskus(®) dry powder combination drugs.

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.