Respiratory diseases represent and important part of daily practice of nearly all physicians. Their incidence, prevalence and significant impact on the quality of life require a substantial attention. In last few decades, the understanding of the pathogenesis of particular diseases allowed focusing the research in the field of therapy on exact components and characteristics of the diseases and modern effective therapies have been developed. The close relationship between experimental, pre-clinical and clinical research is very characteristic for respiratory medicine. The prevalence of certain respiratory diseases is increasing very dramatically and their impact on different aspects of healthcare is evident (morbidity, mortality, economic aspects, quality of life, patients' prognosis, associated complications and comorbidities). Unfortunately, precise and effective tools of disease prevention are not widely available. Therefore, the intensive research in the field of therapy and development of new therapeutic strategies and tools are urgently needed.
This new book summarize the most actual and exciting achievements and successes in the respirology (dominantly pediatric pulmonology) and is focused on the current research in the therapy of bronchial asthma, other respiratory diseases with bronchoobstruction, primary ciliary dyskinesia, sleep apnea syndrome and physiotherapy.
Chapter 1 - During the last few years, only a few new medicaments and compounds have been introduced for the treatment of bronchial asthma. However, the research in this area is dramatic and many potential molecules and compounds are currently under experimental, pre-clinical or even clinical investigations. Better understanding or asthma pathogenesis, associated inflammation and chronic remodeling airway changes in the context of genetic background and environmental impacts are opening new perspectives for the development of novel effective therapies. The chapter summarizes the most actual movements in the area of bronchial asthma therapy with the overview of those compounds, which are currently in clinical investigation and thus will probably enlarge current treatment options, especially for the patients with severe persistent and hard-to-treat form of disease.
Chapter 2 -Nitric oxide (NO) is one of the mostly studied signaling molecules in modern medicine. Under physiological conditions, basal production of NO is responsible for neurotransmission, vasodilatation, bronchodilation and bronchoprotection and acts in various immune processes. In pathological circumstances associated with inflammation of various origin, the production of NO is significantly increased and leads to the over-production of mucus, extravasation of plasma with airway edema, acceleration of inflammatory infiltrates (predominantly T_H2-driven) and through increased formation of reactive nitrogen species causes the oxidative damage to DNA and proteins. Thus, NO plays an important role in many physiological processes, but increased production is typical for certain diseases, e.g. bronchial asthma. Therefore, enzymes associated with the metabolism of NO (inducible NO-synthase, arginase) seem to be an interesting target for anti-asthmatic therapy. In this chapter the authors summarize current knowledge and direction in therapeutic modulation of NO formation and through own original results from animal experiments support the possible application of NO-synthase inhibitors for the treatment of respiratory diseases associated with bronchial hyperreactivity and obstruction.
Chapter 3 - Never-ending story of pediatric gastroenterology and pulmonology is represented by the dilemma about the possible association of bronchial asthma and gastroesophageal reflux (GER). Authors in this chapter provide a critical review of current knowledge based on the recent data from the studies. They analyze, whether there could be any association (and if yes, how it is expressed and how far is it clinically relevant) or if these two entities only coexist with each other. It should be admitted, that causal relationship between GER and asthma has not been clearly explained and still remains unclear, whether the reflux causes asthma, asthma (and certain anti-asthmatic medications) triggers reflux, or both coexists simultaneously in one patients. The chapter provides rationale view on the current diagnostic approach and therapeutic strategy in those asthmatics, in which GER could participate on the respiratory symptoms and disease worsening. The crucial remains the presence of clinical symptoms of GER. Recent double-blinded studies showed that the treatment of asymptomatic GER did not improve asthma control in children. Moreover, long-term use of proton pump inhibitors could have side effects. Therefore, the association of GER and asthma as well therapeutic strategy should be evaluated very carefully in each particular patient.
Chapter 4 - Cough is the most common chronic respiratory symptom across all the age categories and could be associated with a broad spectrum of respiratory and extra-respiratory diseases and conditions. The understanding of different modes of cough induction and the identification of various cough receptors is crucial for developing of effective anti-cough therapies. Moreover, the empirical use of many, especial over-the-counter preparations should have the scientific basis and the understanding of mode of action of each compound is important not only for efficacy confirmation but also for the selection of suitable patient for such therapy. The chapter supplies up-to-date description of different cough receptors and their localization and analyzes the possibilities of the pharmacological modulation of cough reflex through different over-the-counter medications.
Chapter 5 - Syndromes of primary ciliary dyskinesia (PCD) represent an emerging and enlarging area of pulmonology with explosion of knowledge, especially regarding the genetic background of particular form of PCD. In last few years, several PCD causal genes were detected and the morphological and/or functional clinical correlates were described. The chapter provides an interesting view on the clinical picture, genetic reasons and diagnostic approach to the patients with suspected ciliary dyskinesia. The closing part of the chapter analyses current and future possibilities of the therapy of these severe diseases with substantial impact on quality of life and patients' prognosis.
Chapter 6 - Sleep medicine studies the pathological situations emerging during various phases of sleep. Polysomnography has developed into the validated and relevant diagnostic tool for sleep disorders. The chapter analyses the topic of obstructive sleep apnea syndrome in children and showed current diagnostic strategy. Authors present their own experiences with obstructive sleep apnea syndrome and its screening among children. The last part clearly describes current and perspective therapeutic possibilities for affected children.
Chapter 7 - Animal models of respiratory diseases and pathological statuses provide an important mode of research in respirology, regarding etiology, pathophysiology, diagnostic and therapeutic modalities of particular diseases. Chest physiotherapy is an important part of complex respiratory therapy of different acute and chronic diseases. The chapter analyses experimental studies assessing the efficacy and safety of chest physiotherapy techniques and characterizes the challenges in the assessment of mucus clearance in vivo. Authors present also their original results and experiences.
The book brings current view on the characteristics, diagnosis and therapy of the most important entities of pediatric respiratory medicine. The chapters provide a concise view on the current movement in the area of novel therapies. In each chapter, the authors present critical review of the literature data in the context of their own experiences and original results. Assoc. prof. Milos Jesenak, M.D., Ph.D. et Ph.D., MBA. Editor Department of Paediatrics University Hospital in Martin Kollarova 2, 036 59 Martin Slovak Republic Email: jesenak@gmail.com

Preface vii

Acknowledgment xi

Chapter 1 Current Challenges and Perspectives in Bronchial Asthma Therapy 1

Chapter 2 Therapeutic Use of Nitric Oxide Synthase Inhibitors in Respiratory Diseases with Bronchial Hyperreactivity 99

Chapter 3 Gastroesophageal Reflux Disease and Bronchial Asthma in Children - Current Therapeutic Approach 121

Chapter 4 Acute Cough Related to Upper Airway Diseases in Children, Understanding of Mechanisms and Therapeutical Implications 129

Chapter 5 Primary Ciliary Dyskinesia -Current Therapeutic Approach 157

Chapter 6 Obstructive Sleep Apnea Syndrome in Children - The Recent View on the Treatment 177

Chapter 7 Animal Models to Assess the Efficacy and Safety of Chest Physiotherapy Techniques for Critically III Patients 191

Index 201

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