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Biomedical subjects

Petr Pohunek

Publications and source records attributed to Petr Pohunek.

10 recordsLinked to original sources

Can we treat airway remodeling?

Asthma is a chronic disease that has been associated with structural changes of the airway wall. These changes lead to decreased reversibility of airway obstruction and have been understood as poorly reversible. Recent studies have proved that even some of the processes involved in airway remodeling may be reversible with early detection of the disease and appropriate anti inflammatory treatment. New treatments should be directed not only against inflammation itself but also against these chronic changes.

Administration, Inhalation↗

Pediatric asthma: how significant it is for the whole life?

Asthma is most frequent chronic disease in childhood. Childhood asthma frequently persists to adulthood and the available evidence suggests that the severity of childhood asthma predicts the severity of asthma in the adulthood. To prevent long term remodeling of the airways and improve prognosis, early diagnosis and treatment are necessary. More precise markers that would help to detect asthma and predict its prognosis are urgently needed.

Asthma↗

Budesonide/formoterol improves lung function compared with budesonide alone in children with asthma.

UNLABELLED: We aimed to compare the efficacy and safety of budesonide/formoterol (Symbicort) with budesonide alone (Pulmicort) or budesonide (Pulmicort) and formoterol (Oxis) administered via separate inhalers in children with asthma. In a 12 wk, double-blind study, a total of 630 children with asthma (mean age 8 yr [4-11 yr]; mean forced expiratory volume in 1 s (FEV(1)) 92% predicted; mean inhaled corticosteroid dose 454 microg/day) were randomized to: budesonide/formoterol (80/4.5 microg, two inhalations twice daily); a corresponding dose of budesonide alone (100 microg, two inhalations twice daily); or a corresponding dose of budesonide (100 microg, two inhalations twice daily) and formoterol (4.5 microg, two inhalations twice daily) (budesonide + formoterol in separate inhalers). The primary efficacy variable was the change from baseline to treatment (average of the 12-wk treatment period) in morning peak expiratory flow (PEF). Other changes in lung function and asthma symptoms were assessed, as was safety. Budesonide/formoterol significantly improved morning PEF, evening PEF and FEV(1) compared with budesonide (all p < 0.001); there was no significant difference between budesonide/formoterol and budesonide + formoterol in separate inhalers for these variables. All other diary card variables improved from baseline in all treatment groups; there were no significant between-group differences. Adverse-event profiles were similar in all groups; there were no serious asthma-related adverse events in any treatment group. CONCLUSION: budesonide/formoterol significantly improved lung function in children (aged 4-11 yr) with asthma compared with budesonide alone. Budesonide/formoterol is a safe and effective treatment option for children with asthma.

Adrenergic beta-Agonists↗

Differential cytokine profile in children with cystic fibrosis.

The previously observed occurrence of antineutrophil cytoplasmic autoantibodies (ANCA) in patients who have cystic fibrosis (CF), together with the reported decrease in IgG2, a Th1-controlled isotype, suggests a potential for Th1/Th2 imbalance in CF patients with a possible Th2 predominance. 48 CF patients and 16 controls had levels of IFNgamma, IL-4, and IL-10 measured in supernatants of whole blood cell cultures stimulated by lipopolysaccharide (LPS) and phytohemaglutinine (PHA). The patients were divided into 2 groups: "low responders", having negligible secretion of cytokines (IFNgamma: 10.0-200.0 pg/ml, IL-4: 0.0-0.3 pg/ml) and "high responders", producing high levels of both IFNgamma (500.0-2000.0 pg/ml) and IL-4 (1.0-200.0 pg/ml). There was a statistically significant (P < 0.01) deterioration of lung function measured by an FEV(1) decline by 11.2% over 3 years in the "low responder" group. 10 of 16 "low responders" had chronic lung infections with P. aeruginosa while such infection was less prevalent in the "high responder" group where only 13 of 32 CF patients had positive cultures. A shift towards Th2 response was observed in the "high responder" group as children chronically infected with P. aeruginosa had greater IL-4 production than non-infected CF patients within the same cohort. ANCA autoantibodies were found only in the "high responder" group. Th2 immune response predominance in a subset of CF patients is associated with chronic P. aeruginosa infection.

Adolescent↗

Widespread clone of Burkholderia cenocepacia in cystic fibrosis patients in the Czech Republic.

The morbidity and mortality rates in patients with cystic fibrosis (CF) are significantly affected by infections with Burkholderia cepacia complex. In a Czech CF Centre, the prevalence of the infection reached up to 30 %, with the majority of patients found to be infected with Burkholderia cenocepacia (formerly genomovar III of the Burkholderia cepacia complex). Since B. cenocepacia is associated with patient-to-patient transmission and epidemic outbreaks among CF patients, this study sought to examine the epidemiological relatedness between the Czech isolates belonging to the genomovar-homogeneous group. Eighty-three clinical isolates recovered from 67 CF patients were analysed using a random amplified polymorphic DNA (RAPD) assay and macrorestriction typing (SpeI and XbaI) followed by PFGE. A single predominant banding pattern shared by multiple isolates was detected, although SpeI-generated PFGE results yielded a higher rate of inter-pattern variability in comparison to the more uniform RAPD and XbaI-generated PFGE results for this clone. Both typing systems also showed that only three out of 67 patients harboured strains distinct from the major strain type. The dominant clone was characterized by PCR positivity for the B. cepacia epidemic strain marker, PCR negativity for the cable pilin subunit gene and close genetic relatedness to the epidemic strain of RAPD 01 type previously identified in Canada.

Adolescent↗

Development, structure and function of the upper airways.

The upper airways play an essential role in the conduction of air into the lungs, and influence the properties of the inhaled air by both the anatomical structure and the functional properties of the mucosa, cartilages and neural and lymphatic tissues. The upper airways also play an important role in the protection of the lower airways, in the formation of the sound and host the sense of olfaction. Main events in the development of the upper airways happen during early embryonic periods. Postnatally, the growth of the airways follows the growth of the skeleton of the head and of the neck and thorax. Growth is accelerated mainly during the first 2 years of life; thereafter, it linearly follows the growth of the body. For a profound understanding of the function of the upper airways, it is important to understand the main developmental events during both prenatal and postnatal periods.

Airway Obstruction↗

Dose-related efficacy and safety of formoterol (Oxis) Turbuhaler compared with salmeterol Diskhaler in children with asthma.

To compare the dose-related bronchodilator efficacy and tolerability of formoterol (Oxis) Turbuhaler with salmeterol Diskhaler and placebo in children with asthma. A single-dose, randomized, double-blind, incomplete crossover study of 68 children (7-17 years), with moderate-to-severe asthma, 82% receiving inhaled corticosteroids. Patients received four of six treatments [4.5, 9, 18, or 36 microg formoterol (6, 12, 24 or 48 microg metered doses), 50 microg salmeterol (metered dose) or placebo] at 12-h visits, separated by > or =3 days. Forced expiratory volume in 1 s (FEV1), pulse, blood pressure, electrocardiogram, adverse events and urine formoterol were assessed. The therapeutic ratio of formoterol vs. salmeterol was estimated from the efficacy and systemic effects results. All active treatments significantly improved FEV1 compared with placebo. Formoterol 9-36 microg provided dose-related increases over salmeterol in lung function: average 12-h FEV1 (increases of 4.9-8.7%, p < 0.001) and FEV1 at 12 h post-dose (7.0-12.2%, p < 0.001). The onset of effect of formoterol was also significantly faster than salmeterol for doses > or =9 microg. Salmeterol 50 microg was estimated to be equieffective to 3.3 microg formoterol for 12-h average FEV1 and the estimated equieffective dose for a variety of systemic effects was 7.8-13.5 microg formoterol. All treatments were well tolerated. Formoterol (Oxis) Turbuhaler 4.5-36 microg provided dose-related improvements in bronchodilator efficacy in children with asthma. Formoterol > or =9 microg provided superior bronchodilator efficacy over 12 h compared with salmeterol Diskhaler 50 microg with no increase in systemic effects.

Administration, Inhalation↗

Budesonide and formoterol in a single inhaler controls asthma in adolescents.

Despite the availability of effective treatments and national guidelines, morbidity from asthma remains high among adolescents. Adolescents need to be considered as a distinct group of individuals with different requirements to those of children and adults. In particular, their non-adherence to prescribed treatment regimens is of concern and is a significant factor contributing to the high rate of morbidity in adolescents. Studies in children aged 4 to 17 years suggest that the combination of an inhaled corticosteroid (ICS) and a long-acting beta2-agonist effectively controls asthma symptoms in patients who remain symptomatic on ICS alone. In order to improve adherence to therapy, the use of combined therapy with an ICS and a long-acting beta2-agonist in a single inhaler should be considered and the dosing frequency should be adjusted according to the severity of asthma symptoms. This should empower patients with a greater degree of self-management and may be important in helping adolescents feel responsible for the management of their asthma. Results from a recent subanalysis demonstrate that the combination of budesonide and formoterol administered twice daily via a single inhaler (Symbicort Turbuhaler) rapidly gains and maintains control of asthma in adolescents whose asthma is not controlled on ICS alone. It is anticipated that this will lead to improved adherence to therapy in this difficult-to-treat population.

Administration, Inhalation↗