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Aim: To show specific features of respiratory disoders in patients with ischemic heart disease (IHD) and chronic obstructive pulmonary disease (COPD) taking atenolol for a long time., Material and Methods: A long-term study of external respiration function was made in 287 patients with IHD and COPD treated with berodual and atenolol (group 1) vs 74 matched patients taking berodual only., Results: Atenolol treated patients demonstrated more pronounced respiratory disorders. Small respiratory tracts were involved earlier with appearance of expiratory peripheral collapse and early expiratory closure of the respiratory tracts. Diffuse ability of the pulmonary tissue deteriorated. Conclusion. Atenolol has a negative effect on the respiratory system, so it is necessary to control external respiratory function in the course of treatment.

Background and Purpose: Sleep is an active and highly organized biological process that is an important component of life. Self-report measures of sleep provide information that can be useful for characterizing the quality of sleep in subgroups of the population. A 12-item self-report sleep measure, the Medical Outcomes Study Sleep measure, was developed and evaluated previously in a sample of 3445 individuals with chronic illness., Patients and Methods: In this study, we evaluate the psychometric properties of the MOS Sleep measure in a nationally representative sample of 1011 US adults aged 18 and older and in a sample of 173 adults with neuropathic pain participating in a clinical drug trial., Results: The average age of the general population sample was 46; 51% were female and 81% were white. The average age of the sample of adults with neuropathic pain was 72; 53% were female and 95% were white. Internal consistency reliability estimates for the MOS Sleep scales were 0.73 or higher, with the exception of the daytime somnolence scale in the US general population, which was 0.63. At baseline of the clinical trial, the neuropathic pain patients reported significantly more sleep disturbance and daytime somnolence, as well as less quantity and adequacy of sleep than patients in the general US population. The MOS Sleep scales were found to be responsive to change in the clinical trial with statistically significant improvements observed after administration of pregabalin for sleep disturbance (standardized response mean, SRM=-0.76, P=0.0007), shortness of breath (SRM=-0.20, P=0.0302), sleep adequacy (SRM=0.57, P=0.0014), sleep quantity (SRM=0.55, P=0.0086), and sleep problems (SRM=-0.62, P=0.0036)., Conclusions: This study provides further support for the reliability and validity of the MOS Sleep measure. The instrument can be used to assess important aspects of sleep perceived by adults in the general population or participating in clinical studies.

Background: Wheeze is a significant problem in children. There is a gradual trend of switching from oral to inhaled bronchodilator therapy. No randomised trials have been carried out in the community to compare the clinical outcome of two modes of therapy. If outcome with oral and inhaled bronchodilators is the same in young wheezers in developing countries, it will be easier to manage them., Methods: In a randomised multicentre trial, wheezy children aged 1-59 months with fast breathing and/or lower chest indrawing received oral or inhaled salbutamol at home after responding to up to three cycles of inhaled bronchodilators. They were re-assessed on days 3 and 5 for clinical outcome., Results: From May 2001 to August 2002, 780 children were enrolled; 390 each were randomised to oral and inhaled salbutamol. On day 5, 324 (83.1%) children in the oral and 328 (84.1%) in the inhaled group were completely well. There were no differences in clinical outcome of both modes of therapy., Conclusions: The clinical outcome of children aged 1-59 months with wheeze is similar when treated with oral or inhaled salbutamol. Acute respiratory infection control programmes in developing countries should continue to use oral bronchodilators for the management of wheeze to save both time and money.

There are relatively few studies of albumin use in neonates and children, with most showing no consistent benefit compared with the use of crystalloid solutions. Certainly, albumin treatment is not indicated for treatment of hypoalbuminemia alone. Studies also show that albumin is not indicated in neonates for the initial treatment of hypotension, respiratory distress, or partial exchange transfusions. In adults, albumin is not considered to be the initial therapy for hypovolemia, burn injury, or nutritional supplementation. Based on the evidence, albumin should be used rarely in the neonatal ICU. Albumin may be indicated in the treatment of hypovolemia only after crystalloid infusion has failed. In patients with acute hemorrhagic shock, albumin may be used with crystalloids when blood products are not available immediately. Inpatients with acute or continuing losses of albumin and normal capillary permeability and lymphatic function, such as during persistent thoracostomy tube or surgical site drainage, albumin supplementation will prevent the development of hypoalbuminemia, and possibly edema formation. This has not been studied systematically, however. In patients with hypoalbuminemia and increased capillary permeability, albumin supplementation often leads to greater albumin leakage across the capillary membrane, contributing to edema formation without improvement in outcome. As the disease process improves and capillary permeability normalizes, albumin supplementation may accelerate recovery, but long-term benefits of albumin treatment usually cannot be demonstrated. These patients will recover whether or not albumin is administered.

Objective: The benefits of helium-oxygen (heliox) administration for pediatric upper and lower respiratory disorders have been well described. However, while most studies advocate delivery via a sealed or semisealed facemask system, such systems may not be tolerated in the young child. This report describes the successful and efficacious delivery of heliox via nasal cannula to 5 infants., Methods: A mixture of 80% helium/20% oxygen was blended with 100% oxygen from a wall source and delivered via nasal cannula to 5 spontaneously breathing infants with respiratory distress at flow rates of 2 to 3 liters per minute. Treatment efficacy was retrospectively extracted from nursing, respiratory therapist, and physician entries in the medical record, specifically focusing on changes in respiratory rate, work of breathing, and oxygenation and/or ventilation parameters., Results: All 5 infants tolerated the nasal cannula well. In 2, nasal cannulae were used after attempts to use a facemask system were not tolerated. All patients demonstrated rapid improvements in respiratory parameters including a decreased work of breathing (n = 5), respiratory rate (n = 4), transcutaneous CO2 (n = 2), and stridor (n = 2), or improved oxygenation (n = 1). In 1 patient, the recurrence of distress shortly after discontinuing heliox was rapidly reversed with heliox reinstitution., Conclusions: In infants with respiratory distress who do not tolerate a facemask, the use of nasal cannula represents a viable and efficacious alternative for heliox delivery.

Rett syndrome, a neurodevelopmental disorder, manifests in the first few years of life with developmental arrest, stereotyped behaviors, and respiratory abnormalities. Seizures occur in 70 to 80% of patients. Clinical drug trials have not demonstrated the superiority of any specific antiepilepsy drug. We report our experience with topiramate in eight patients with Rett syndrome. Topiramate was initiated as monotherapy in two patients and as adjunctive therapy in six patients. Seven patients had improved seizure control. Respiratory abnormalities improved by 50 to 75% in two patients and by 20 to 50% in two others. In our cohort, seven of eight patients showed improvement in seizure control and/or respiratory abnormalities on topiramate. Topiramate was well tolerated. The effect of topiramate, a broad-spectrum drug, could be due to its gamma-aminobutyric acid (GABA)ergic and glutaminergic effects, both systems thought to be disordered in Rett syndrome.

Objective: Clonidine, which inhibits locus coeruleus discharge, would seem for theoretical reasons to be a good antipanic drug. Panic disorder (PD) presents a heterogeneous cluster of symptoms and a classification based on subtypes has been suggested and the respiratory symptoms group appears as a distinct subtype., Method: We report three cases of respiratory PD patients who were successfully treated with clonidine., Results: Patients obtained panic free status, reduced anxiety levels and better functioning after clonidine administration (0.30-0.45 mg/day) for 6 weeks., Conclusion: Clonidine can be effective in the treatment of respiratory PD. This drug might play a role in relieving symptoms of anxiety due to noradrenergic hyperactivity in these patients.

Influenza viruses are one of the leading causes of morbidity and mortality during winter months. Increased respiratory rate (tachypnea) is a sign of increasing lower respiratory disease during influenza infection and is frequently observed in hospitalized patients. We investigated this clinical sign in influenza virus-infected cotton rats (Sigmodon hispidus) and the efficacy of antiviral and anti-inflammatory therapy in reducing symptomatic disease. Cotton rats infected intranasally with A/Wuhan/359/95 (H3N2) had increased respiratory rates from 1 to 4 days postinfection that correlated with the dose of virus used to inoculate the animal but not the amount of virus recovered from the lung. In addition, evaluation of sequential lung tissue pathology revealed that extensive epithelial cell destruction of small airways correlated with tachypnea. Increased respiratory rate was not observed in immune animals, supporting results that demonstrated a requirement for exposure to, and infection by, large amounts of live virus for induction of tachypnea. A variety of therapeutic approaches proved ineffective in reducing tachypnea, including anti-inflammatory therapy with systemic triamcinolone acetonide, bronchodilatory therapy with levalbuterol, or antiviral therapy with zanamivir. These results, together with the pathologic observations, suggest that early disruption of the lower respiratory tract epithelium is a major component of the pathophysiology of influenza infection. Therapeutic approaches need to be tailored to clear airway obstruction and restore an intact epithelium.

It has been shown that the leukotriens play a role in the pathobiologic process of allergic asthma and wheezing due to infection. Their specific role in other respiratory disorders or in other diseases is not yet fully understood. A recent consensus has elaborated the guidelines for the treatment of asthma in the paediatric age. According to these guidelines, the leukotriene-antagonists are recommended as a possible alternative to inhaled corticosteroids in the long-term treatment of mild persistent asthma. The association of antileukotrienes with the usual classical therapy led to a great improvement in the treatment of the most severe forms of the disease. Moreover, a growing number of disorders such as allergic rhinitis, chronic urticaria, atopic dermatitis and nasal polyposis seem to benefit from the use of these new drugs. In allergic rhinitis, the most common allergic disorder, the leukotrienes seem to be, together with histamine, important mediators of both the early and late stage of the allergic reaction. They seem to be responsible for the vasodilation and therefore for the nasal obstruction. There is a production of leukotrienes also in chronic urticaria, which is more frequent in adults, and in atopic dermatitis, which usually has its onset in the paediatric age. This paper summarizes the results of several clinical trials evaluating the therapeutical efficacy and safety of the leukotriene-antagonists. Despite the promising results, further studies are however necessary on a greater number of patients before recommending the use of this type of drug in this kind of disorders.

Working out formula and techology of producing the syrup, which is based on herbs of Far Eastern Region (dog rose; leaves of currant, lime-tree; herbs St. John's wort, parsley. Nettle; licorice) and food dietary supplements--Laminal (the product of processing of brown seaweeds). Here are the results of the research work of chemical contents, energetic value, minor componential contents and microbiological values of syrup. The results of approbation of the syrup on the group of children (who catch a cold very often) showed the increase of coefficient of special immune lymphocytic-monocytical and cell-phagocytal protection. These results allow us to recommend it as a kind of treatment, included in health-improvement program.

Circadian variations of external respiratory parameters were determined in 44 patients with different forms of pulmonary tuberculosis. Salbutamol inhalation tests were performed at 6 a.m. and p.m. Worse patency of the bronchial tree was diagnosed in the evening than in the afternoon, which should be taken into account in distributing a daily dose of beta2-receptor agonists.

The goal of the study was to describe with prospective methodology the therapeutic response to nortriptyline in the respiratory panic disorder (PD) subtype versus the non-respiratory subtype. A total of 118 PD outpatients (DSM-IV) were previously divided into respiratory (n=77) and non-respiratory (n=41) subtypes and then treated with nortriptyline for 1 year. Demographic and clinical features were compared in the two groups. Anxiety scales were administered before and during the treatment by raters who were blind to the subtype diagnosis. The principal instruments used to evaluate response were the Clinical Global Impression, the Sheehan Panic and Anticipatory Anxiety Scale, and the Panic Disorder Severity Scale. In the first 8 weeks of treatment (acute phase), the respiratory subtype had a significantly faster response on all the major scales. At the end of the study (week 52), there was no difference in the scale scores, and the reduction in panic attacks from baseline to end-point did not differ significantly between the two groups. In the respiratory subtype, the disorder had a later onset, was associated with a high familial history of mental disorder, and significantly more often required treatment with more than an occasional benzodiazepine. The non-respiratory subtype had significantly more previous depressive episodes. In conclusion, the respiratory PD subtype had a faster response to treatment with nortriptyline at 8 weeks than did the non-respiratory subtype, and an equivalent response after 1 year of treatment.

Objective: To assess the influence of acute alpha and beta blockade on ventilation and symptoms of breathlessness during exercise in patients with chronic heart failure and in controls., Methods: 11 patients with chronic heart failure and 11 control subjects underwent repeated exercise testing with metabolic gas exchange after random, double blind administration of either an alpha blocker and placebo, a beta blocker and a placebo, both an alpha blocker and a beta blocker, or double placebo., Results: Patients had a lower peak oxygen consumption (mean (SD) 20.7 (4.9) v 37.6 (9.6) ml/kg/min, p < 0.0001) and a steeper slope relating ventilation to carbon dioxide production (VE/CO2 slope) (26.5 (4.1) v 37.1 (8.2), p = 0.0011), than controls. Blood pressure was lower following alpha and beta blockade (p < 0.05) and the gradients of the slopes relating heart rate to oxygen consumption following the beta blocker were reduced (p < 0.05). Exercise time and peak ventilatory variables following beta or alpha blockers were unchanged. Ventilation was reduced during submaximal exercise following the active medications. Combined alpha and beta blockade produced the greatest difference (p < 0.005), but the alpha and beta blockers alone also reduced ventilation (p < 0.05). There was no difference in perceived exertion during exercise with any of the treatments., Conclusion: Acute sympathetic inhibition can reduce submaximal ventilation during exercise in patients with heart failure and control subjects, suggesting that autonomic nervous system activation has an important role in the abnormal ventilatory response to exercise in chronic heart failure.

All-trans retinoic acid (ATRA) is a potent differentiation agent that is effective therapy in acute promyelocytic leukaemia. Although ATRA is generally well tolerated, some patients develop retinoic acid syndrome. This syndrome is manifested by unexplained fever, weight gain, respiratory distress, interstitial pulmonary infiltrates, pleural and pericardial effusion, episodic hypotension, and acute renal failure. However, if identified early enough, effective therapy can be administered. This chapter discusses the clinical aspects and pathogenesis of retinoic acid syndrome.

We report a case of latex anaphylactoid reaction in a 39-year-old man with aortitis. He was scheduled to undergo stent-graft implantation. When the operation progressed into his abdomen, respiratory symptoms, wheezing and high airway pressure, occurred. However, he did not show any dermal symptoms. Thirty-five minutes after the start of respiratory symptoms, his face suddenly showed flush, and intravenous epinephrine worked successfully against anaphylactoid reactions. There are anaphylactoid reactions which occurred with respiratory symptoms, and we should be aware of these cases.

Context: This study makes a comparison between two subtypes of panic disorder regarding the clinical efficacy of clonazepam, a benzodiazepine., Objectives: To evaluate the clinical efficacy of clonazepam in a fixed dosage (2 mg/day), compared to placebo, in the treatment of panic disorder patients and to verify whether there are any differences in the responses to clonazepam between panic disorder patients with the respiratory and non-respiratory subtypes., Type of Study: Randomized study with clonazepam and placebo., Setting: Outpatient Anxiety and Depression Unit of the Institute of Psychiatry, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil., Participants: 34 patients with a diagnosis of panic disorder with agoraphobia, between 18 and 55 years old., Procedures: Administration of clonazepam or placebo for 6 weeks, in panic disorder patients, after they were classified within two subtypes of panic disorder: respiratory and non-respiratory., Main Measurements: Changes in the number of panic attacks in comparison with the period before the beginning of the study; Hamilton Anxiety Scale; Global Clinical Impression Scale; and Patient's Global Impression scale., Results: In the group that received clonazepam, by the end of the 6th week there was a statistically significant clinical improvement, shown by the remission of panic attacks (p < 0.001) and decrease in anxiety (p = 0.024). In the group that received clonazepam there was no significant difference between the respiratory and non-respiratory subtypes of panic disorder, regarding the therapeutic response to clonazepam., Conclusion: Clonazepam was equally effective in the treatment of the respiratory and non-respiratory subtypes of panic disorder, suggesting there is no difference in the therapeutic response between the two subtypes.

Background: In the context of increasing attention to medical errors, missed therapies have become a subject of focus both for optimizing clinical care and for assuring appropriate institutional performance during external review by accrediting bodies. Because the issue of missed treatments in respiratory therapy has received little attention to date, we undertook to describe the frequency and causes of missed respiratory therapy bronchodilator medication treatments at the Cleveland Clinic Hospital., Methods: Between August 2000 and August 2001, using a respiratory therapy management information system, we recorded the number of respiratory therapy bronchodilator medication treatments ordered and delivered (via small-volume nebulizer and metered-dose inhaler) and the reason(s) for each missed treatment., Results: Over the 12-month study interval 113,554 bronchodilator medication treatments (74,921 via small-volume nebulizer and 38,633 via metered-dose inhaler) were ordered. Overall, 4,012 medication treatments were missed (3.5% of the total), with variation by month ranging from 2.0% to 5.0%. The commonest reason for failure to administer the ordered bronchodilator treatment was the patient being out of the room at the time of the therapist's visit, which accounted for nearly one third of missed therapies. Next most common was the patient refusing treatment (24.6%), followed by the patient being unavailable because of ongoing activities or therapy (eg, physical therapy or a medical procedure). The least common reason was the respiratory therapist being called away to administer therapy to another patient (1.4%)., Conclusions: Overall, the frequency of missed bronchodilator treatments was relatively low in this series. The next steps include developing strategies to lower the frequency of missed treatments, so as to optimize the allocation of respiratory therapy services, and studying the clinical consequences of missed therapies.

Objective: To get a comprehensive recognition about the profile of phrenic repetitive nerve stimulation (PRNS) and intercostal repetitive nerve stimulation (IRNS) in healthy people, to investigate the electrophysiological features about respiratory function of myasthenia gravis (MG) patients, and to detect the predictive value of IRNS and PRNS on the respiratory deterioration of MG patients during the pulse treatment with large dosage of adrenal corticosteroid., Subjects and Methods: Bilateral PRNS and IRNS with stimulation frequency of 3 and 5 Hz were tested in 28 healthy people and 113 MG patients; limb and cranial repetitive nerve stimulation (RNS), clinical score and forced vital capacity (FVC) were also recorded from those MG patients. Further more, PRNS and IRNS of 36 MG patients were tested 3 days before the beginning of their adrenal corticosteroid pulse treatment, FVC, clinical score and respiratory changes of the MG patients were simultaneously observed., Results: For healthy people, there were no significant differences in the results of PRNS or IRNS in different age, sex and testing sides. After combining the left result with the right one, the amplitude decrement percentage in PRNS and IRNS was less than 7%. PRNS had more technical difficulty than IRNS. For 113 MG patients, FVC was dependent on the values of PRNS, IRNS and facial RNS. A subclinical respiratory dysfunction was found in patients with type I and II MG. The abnormal rate of PRNS in type IIb MG was similar to that in type III and IV MG, even though a difference in the percentage of amplitude decrement between them was observed. Meanwhile, both the abnormal rate and the percentage of amplitude decrement of IRNS had no difference between type IIb MG and type III and IV MG. The general incidence of abnormal PRNS and abnormal IRNS were higher than those of decreased FVC and clinical dyspnea, and the sensitivity of PRNS in type IIa MG patients was higher than that of IRNS. Among 36 MG patients under the adrenal corticosteroid pulse treatment, 14 showed the newly clinical dyspnea or worsened original one 2 to 13 days after the beginning of the therapy. There were significant difference of the above parameters between the patients with and without respiratory deterioration during the treatment. Logistic regression analysis showed that when the mean value of the bilateral IRNS amplitude decrement was larger than 30%, the odds ratio of the occurrence of the respiratory deterioration was 19.523, for both 3 and 5 Hz stimulation., Conclusions: It is recommended that PRNS and IRNS will be defined as abnormal when their amplitude reduces more than 15%. PRNS and IRNS are neurophysiological indices reflecting the damage of respiratory muscles in MG, they are helpful in evaluating the clinical condition correctly and making the classification of MG properly. It is necessary to test the PRNS and IRNS in type II MG patients regularly. Although the respiratory damage during the adrenal corticosteroid treatment was correlated with PRNS, IRNS, FVC, MG clinical score and type, only IRNS had predictive value on the respiratory deterioration during the treatment.

Background: The effect of respiratory medications on risk of asthma death in the UK was studied using the General Practice Research Database., Methods: A total of 96 258 individuals with a diagnosis of asthma were identified, 43 of whom had died as a result of their asthma. For each case 20 controls were selected. Relative risk (RR) estimates and 95% confidence intervals (CI) were computed for each respiratory drug category controlling for effects of age, sex, body mass index, smoking, frequency of visits to the GP, hospital admissions for asthma, and visits to a specialist., Results: The strongest associations were found for at least 13 prescriptions of short acting beta agonists during the previous year (RR=51.6, 95% CI 7.9 to 345) and 7-12 prescriptions of short acting beta agonists (RR=16.2, 95% CI 2.6 to 101). Short acting beta agonists and inhaled steroids tended to be prescribed most frequently to the same patients. In patients who received more than one prescription per month of short acting beta agonists during the previous year, regular use of inhaled steroids was associated with a 60% reduced risk of asthma death (RR=0.4, 95% CI 0.2 to 1.0)., Conclusions: Regular use of inhaled steroids is associated with a decreased risk of asthma death, and excessive use of short acting beta agonists is associated with a markedly increased risk of asthma death.

EpiGenesis, in collaboration with Taisho and Chiesi, is developing EPI-2010, a 21-mer phosphorothioate respirable antisense oligonucleotide (RASON) that blocks the synthesis of the adenosine A1 receptor, for the potential treatment of asthma.

Respiratory problems are an important issue in the palliative care setting, not only from a diagnostic and therapeutic point of view but also from emotion-related aspects involving both the patients and their families and also caregivers. In this paper we consider some of the most common respiratory problems, such as dyspnea, infections, hemoptysis, hiccup. A review of the literature was performed with reference to the frequency, diagnosis and management of the above respiratory problems in patients in advanced and terminal stages of the disease. Particular emphasis was given to the importance of communication with the patients and their families, which is considered a crucial point in the care and the cure of such patients.

Negative correlation between serum IgE levels and production of IFN-gamma by lymphocytes and positive correlation between serum IgE levels and production of IL-4 by lymphocytes was detected in 12 children with allergic asthma and recurrent respiratory diseases. Deficiency of reduced glutathione in whole blood and some disorders in phagocytic and oxidative burst activity of monocytes were observed in these children. Use of reduced glutathione, L-cysteine and anthocyane (Recancostat, Clear Vision, Switzerland) resulted in elevation of IFN-gamma production, lymphocyte response to mitogens, NK cell activity, increase in percentage of naive CD4(+) T lymphocytes (refreshment effect) and improvement of clinical status. Positive clinical results were lasted during 6 months.

Asthma is diagnosed frequently in patients with respiratory distress. However, laryngeal dysfunction, a common cause of dyspnea, may masquerade as asthma. This study investigated 158 consecutive patients referred to an allergy practice with a diagnosis of asthma. Pulmonary function testing with flow volume loops were used to separate the patients into four groups. These groups consisted of patients with asthma alone in 32%, asthma and laryngeal dysfunction in 16%, laryngeal dysfunction in 26%, and another group not meeting these criteria in 25%. Thirty patients, 10 each from the first three groups, were treated with antireflux medication and reevaluated. Symptom evaluation observed inspiratory difficulties in 73% of the laryngeal dysfunction group compared with 2% of the asthma group (p < 0.0001). Expiratory problems were present in 7% of the laryngeal dysfunction group and 71% of the asthma group (p < 0.0001). The laryngeal dysfunction group only had a 29% beneficial response to Albuterol inhalation compared with a 92% response in the asthma group (p < 0.0001). The laryngeal dysfunction group responded significantly less to both inhaled and oral steroids (p = 0.002). Among the 30 patients treated with antireflux medications, the peak flows improved by 38.7% in the laryngeal dysfunction group compared with 14.8% in the asthma group (p = 0.01).

Background: Transient tachypnea of the newborn results from delayed clearance of lung liquid and is a common cause of admission of full term infants to neonatal intensive care units. The condition is particularly common after elective Caesarean section. Conventional treatment involves appropriate oxygen administration and continuous positive airway pressure in some cases. Most infants receive antibiotic therapy. Hastening the clearance of lung liquid should shorten the duration of the symptoms and reduce complications., Objectives: To determine whether furosemide reduces the duration of oxygen therapy and respiratory symptoms and shortens hospital stay in term infants with transient tachypnea of the newborn., Search Strategy: We searched the Cochrane Controlled Trials Register, PubMed and EMBASE. The primary author and experts in the field were contacted., Selection Criteria: Randomised or quasi-randomised controlled trials. Infants of less than 7 days of age, born after 37 or more weeks of gestation with the clinical picture of transient tachypnea of the newborn. Intravenous, oral or nebulized furosemide compared to placebo or no diuretic in the first 7 days., Data Collection and Analysis: Two reviewers assessed trial quality in each potentially eligible manuscript and two reviewers extracted data., Main Results: Searching revealed only one randomised trial which was methodologically sound. This recruited 50 infants with transient tachypnea. Infants were randomised to receive oral furosemide 2 mg/kg followed by 1 mg/kg 12 hours later, or placebo. Weight loss in the first 24 hours was greater in the furosemide treated group but there was no evidence of a difference between the groups in duration of tachypnea or severity of symptoms or length of hospitalization. The study was methodologically satisfactory., Reviewer's Conclusions: Oral furosemide cannot be recommended as treatment for transient tachypnea of the newborn and it should not be used unless additional data become available. The question remains as to whether intravenous furosemide given to the infant (or even to the mother before Caesarean section) might shorten the duration of the illness. As elective Caesarean section continues at a high level, these two interventions might be worthy of trials.

The availability of a draft sequence for the human genome will revolutionise research into airway disease. This review deals with two of the most important areas impinging on the treatment of patients: pharmacogenetics and pharmacogenomics. Considerable inter-individual variation exists at the DNA level in targets for medication, and variability in response to treatment may, in part, be determined by this genetic variation. Increased knowledge about the human genome might also permit the identification of novel therapeutic targets by expression profiling at the RNA (genomics) or protein (proteomics) level. This review describes recent advances in pharmacogenetics and pharmacogenomics with regard to airway disease.

Treatment strategies in Rett syndrome so far have been essentially symptomatic and supportive. In order to establish the medium-term effects of L-carnitine, an open label trial was performed in a cohort of 21 Rett syndrome females, with a control group of 62 Rett syndrome females of a similar age, for a 6-month period. Compared with the Rett syndrome controls, treatment with L-carnitine led to significant improvements in sleep efficiency (P=0.027), especially in the subjects with a baseline sleep efficiency less than 90%, energy level (P<0.005) and communication skills (P=0.004). There was no significant difference in the subject's level of physical activity, hand function or in the quality of life of the subject's parents. In addition, before and after comparisons of the treatment group showed improvements in expressive speech (P=0.011). Treatment with L-carnitine seems to be of significant benefit in a subgroup of girls with Rett syndrome. In these girls, small but discernible improvements may be of considerable importance to their parents and carers.

The abnormal metabolism of serotonin during the perinatal period alters respiratory network maturation at birth as revealed by comparing the monoamine oxidase A-deficient transgenic (Tg8) with the control (C3H) mice (Bou-Flores et al., 2000). To know whether these alterations occur only transiently or induce persistent respiratory dysfunction during adulthood, we studied the respiratory activity and regulations in adult C3H and Tg8 mice. First, plethysmographic and pneumotachographic analyses of breathing patterns revealed weaker tidal volumes and shorter inspiratory durations in Tg8 than in C3H mice. Second, electrophysiological studies showed that the firing activity of inspiratory medullary neurons and phrenic motoneurons is higher in Tg8 mice and that of the intercostal motoneurons in C3H mice. Third, histological studies indicated abnormally large cell bodies of Tg8 intercostal but not phrenic motoneurons. Finally, respiratory responses to hypoxia and lung inflation are weaker in Tg8 than in C3H mice. dl-p-chlorophenyl-alanine treatments applied to Tg8 mice depress the high serotonin level present during adulthood; the treated mice recover normal respiratory responses to both hypoxia and lung inflation, but their breathing parameters are not significantly affected. Therefore in Tg8 mice the high serotonin level occurring during the perinatal period alters respiratory network maturation and produces a permanent respiratory dysfunction, whereas the high serotonin level present in adults alters the respiratory regulatory processes. In conclusion, the metabolism of serotonin plays a crucial role in the maturation of the respiratory network and in both the respiratory activity and the respiratory regulations.

Rats were exposed for 1 h to increasing concentrations of cadmium (Cd) through inhalation of cadmium chloride aerosol using nose-only inhalation chambers and depositions of Cd in lungs, liver and kidneys were measured. Changes in spontaneous locomotor activities were recorded 2 and 7 d after cessation of exposure. A concentration dependent increase in Cd in lungs, liver and kidneys was accompanied by significant alterations in spontaneous locomotor response that was dependent on the air Cd concentrations and the postexposure duration. The study shows decreased spontaneous locomotor activity due to Cd accumulation in tissues.

Objectives: Acute experimental pancreatitis (induced by cerulein) recently has been reported to cause marked diaphragmatic dysfunction, which may contribute to respiratory distress in this setting. In cerulein-induced acute pancreatitis, expression of inducible nitric oxide synthase is induced to produce a large amount of nitric oxide. Nitric oxide excessively produced has been implicated in diaphragmatic dysfunction induced by a variety of etiologies. The aims of the current study were, first, to examine whether nitric oxide overproduced through inducible nitric oxide synthase is involved in cerulein-induced impairment of diaphragmatic function, and second, if demonstrated, to assess effects of ONO-1714, an inducible nitric oxide synthase inhibitor, on diaphragmatic dysfunction associated with cerulein-induced acute pancreatitis., Design: Prospective, randomized animal study., Setting: University research laboratory., Subjects: Ninety-one male Sprague-Dawley rats, weighing 200-250 g., Interventions: Rats were randomly divided into seven groups (n = 8 each): CONT-SAL, CAER-SAL, CONT-ONO, CAER-DEX, CAER-AMI, CAER-ONOhigh, and CAER-ONOlow. Groups labeled CAER received two consecutive intraperitoneal doses (50 microg/kg) of cerulein, whereas groups labeled CONT received two consecutive intraperitoneal injections of saline. Groups labeled SAL received intraperitoneal saline before cerulein or saline. The group labeled DEX received 2 mg/kg intraperitoneal dexamethasone, and the group labeled AMI received 100 mg/kg intraperitoneal aminoguanidine. The groups labeled ONO, ONOhigh, and ONOlow received ONO-1714 at 0.1 mg/kg, 0.1 mg/kg, and 0.03 mg/kg, respectively, before cerulein or saline., Measurements and Main Results: Diaphragmatic contractility and fatigability were assessed in vitro by using muscle strips excised from the costal diaphragms 6 hrs after the first dose of cerulein or saline. Expression of inducible nitric oxide synthase protein in the diaphragm was assessed by immunohistochemistry by using anti-inducible nitric oxide synthase antibody. Plasma concentrations of nitrite plus nitrate and diaphragmatic concentrations of malondialdehyde were measured. With another set of rats (n = 5 each group), diaphragmatic inducible nitric oxide synthase activity was determined. Twitch and tetanic tensions and tensions generated during fatigue trial were lower in group CAER-SAL than in group CONT-SAL. Cerulein increased diaphragmatic malondialdehyde and plasma nitrite plus nitrate concentrations. Positive immunostaining for inducible nitric oxide synthase protein was found in group CAER-SAL. Dexamethasone and aminoguanidine attenuated the diaphragmatic mechanical damages. A high dose of ONO-1714 attenuated cerulein-induced impairment of diaphragmatic contractility and endurance capacity, although a low dose of the drug failed to do so., Conclusions: Cerulein-induced diaphragmatic dysfunction was attributable, in part, to nitric oxide overproduced via inducible nitric oxide synthase. Pretreatment with ONO-1714 at a dose of 0.1 mg/kg attenuated diaphragmatic dysfunction associated with cerulein-induced pancreatitis in rats assessed by contractile profiles and endurance capacity. This beneficial effect of ONO-1714 may be attributable, in part, to inhibition of diaphragmatic lipid peroxidation induced by nitric oxide-derived free radicals.

Background: Pharyngeal pH monitoring is a diagnostic tool used to identify Gastroesophageal reflux disease (GERD) as an etiology of respiratory symptoms. We performed pharyngeal pH monitoring on 14 patients with respiratory symptoms thought to be induced by GERD., Methods: Symptoms and pH monitoring (esophageal and pharyngeal) were assessed prior to and 3 months after the initiation of double-dose proton pump inhibitor therapy., Results: Symptoms included cough, hoarseness, and throat clearing. Ten patients had at least one episode of pharyngeal reflux (PR+) and 4 patients had no pharyngeal reflux (PR-). Pharyngeal reflux episodes in PR+ patients decreased from 3.5 to 0.9 (P <0.05) per day with 8 of 10 (80%) patients having elimination or reduction of such episodes. Eight of 9 PR+ patients (89%) with suppressed pharyngeal reflux on medical therapy had resolution of respiratory symptoms. Three of 4 PR- patients (75%) had persistent symptoms on medical therapy., Conclusions: Proton pump inhibitor therapy improves clinical symptoms and decreases pharyngeal reflux episodes in patients with respiratory symptoms related to GERD. Direct measurement of pharyngeal pH is helpful in the identification of patients likely to respond to antireflux therapy.

At patients threatened with premature childbirth the influence of glicocorticoids on short and tong-term fetal heart rate variability and the occurrence of respiratory arrhythmia was evaluated. It has been ascertained statistical significant lowering of the incidence of fetal respiratory arrhythmia and short-term variability. Described changes had a temporary character and surrendered of normalization in the course 72 of hours after last use of glicocorticoids. The influence of glicocorticoids on select biochemical and biophysical parameters of state pregnant women was also studied. One specified occurrence of incidental symptoms in road drove of therapy. Pregnant women in road of treatment glicocorticoids have also observed a temporary weakness of feeling of fetal movements.

Unlabelled: Sepsis causes impairment of diaphragmatic contractility and endurance capacity. Nitric oxide (NO) produced via inducible NO synthase (iNOS) has been implicated in the pathogenesis. Peroxynitrite, a NO-derived powerful oxidant, may be responsible for infection-induced diaphragmatic muscle failure. Therefore, we examined whether ONO1714, a new selective iNOS inhibitor, prevents sepsis-induced diaphragmatic dysfunction. Fifty male Golden-Syrian hamsters were randomly divided into five groups: hamsters that underwent sham laparotomy alone and received saline injection (Group Sham), those that underwent cecal ligation with puncture (CLP) and received saline injection (Group Sepsis), those that underwent sham laparotomy and received injection of ONO1714 0.3 mg/kg (Group Sham-ONO1714high), those that underwent CLP and received ONO1714 0.1 mg/kg (Group Sepsis-ONO1714low), and those that underwent CLP and received ONO1714 0.3 mg/kg (Group Sepsis-ONO1714high). ONO1714 or saline was intraperitoneally injected 10 min before surgery. Diaphragmatic contractility was assessed in vitro using diaphragm muscle strips excised 24 h after operation. Diaphragm fatigability was assessed by time until tension decreased to 50% of the initial value (T50%) during fatigue trials. Twitch, tetanic tensions, and T50% during fatigue trials were reduced in Group Sepsis. Pretreatment with ONO1714 dose-dependently attenuated sepsis-induced diaphragmatic contractile profiles and endurance capacity. CLP increased plasma nitrite/nitrate (NOx; stable NO metabolites), and diaphragm malondialdehyde (MDA; a product of lipid peroxidation), positive immunostaining for nitrotyrosine (peroxynitrite footprint), and iNOS activity. ONO1714 attenuated the increase. This beneficial effect of ONO1714 may be attributable, in part, to inhibition of peroxynitrite-induced lipid peroxidation in the diaphragm., Implications: Sepsis impairs diaphragmatic contractility and endurance capacity, which may be involved in acute respiratory failure. Pretreatment with ONO1714, a new selective inducible nitric oxide synthase inhibitor, attenuated sepsis-induced diaphragmatic dysfunction in hamsters.

The paper provides evidence for the pathogenetic approach to treating acute lung lesion (ALL) and adult respiratory distress syndrome (ARDS). An algorithm of the use of Russian lung surfactant preparations: CT-HL and CT-BL has been developed. In involves earlier (the first days following the onset of respiratory failure) use of surfactant, its combined bolus intratracheal or intrabronchial administration in doses of 200-400 mg/m2, followed by continuous (5-day) aerosol inhalation in doses of 20-30 mg/h for children and 30-75 mg/h for adults until pronounced clinical and X-ray effects are shown. Fifty three patients were found to develop ALL and ARDS in the presence of severe pneumonia, postperfusion lung disorders, reperfusion syndrome, pulmonary embolism, long-term artificial ventilation, combined car accident injury and gunshot wounds of the chest, heroine intoxication, septic shock, sepsis, postoperative sequels in cancer patients, and after hepatic transplantation or massive aspiration of gastric contents. Fifty patients were overcome their critical status, 44 survived. The duration of artificial ventilation (AV) ranged from 1 to 6 days. Earlier use of the drugs made it possible to transfer patients to safe AV regimens and to eliminate ALL and ARDS rapidly and to significantly reduce mortality due to critical states.

Respirable antisense oligonucleotides (RASONs), which attenuate specific disease-associated mRNAs, represent a new class of respiratory therapeutics with considerable potential. RASONs overcome previous obstacles that have impeded the development of antisense therapeutics targeting diseases in other organ systems. RASONs are delivered directly to the target tissue via inhalation; their uptake seems to be enhanced by cationic properties inherent in pulmonary surfactant, and, because of the markedly different target properties of mRNA and proteins, they can have very long durations of effect compared with traditional drugs targeting the protein of the same gene. RASONs contain chemical modifications that decrease their degradation by cellular nucleases. However, total insensitivity to nucleases is probably not an optimal design criterion for RASONs, because moderate nuclease sensitivity can prevent their systemic delivery, decreasing the potential for systemic toxicity. EPI-2010 is a 21-mer phosphorothioate RASON that attenuates bronchoconstriction, inflammation and surfactant depletion in preclinical models of human asthma, has a duration of effect of seven days, and seems to undergo minimal systemic delivery.

A 1-year-old boy with cerebrospinal trypanosomiasis presented with severe respiratory symptoms, hepatosplenomegaly and no neurological signs of trypanosomiasis. Agitation and high fever on the 2nd day in hospital prompted a lumbar puncture and trypanosomes were recovered from the cerebrospinal fluid.

Identification of the determinants of efficient aerosol delivery and the specific challenges of aerosol delivery to infants and children can facilitate a systematic approach to optimize aerosol delivery to this population. There are inherent anatomical, physiologic, pathophysiologic, and technical limitations of aerosol efficiency in infants and young children. Nevertheless, one can enhance aerosol efficiency through application of sound principles of aerosol delivery and by exerting control over factors that are amenable to intervention. Improvements in aerosol formulations and delivery systems are being made that will enhance efficiency, decrease risk, and reduce waste and cost. Attention to aerosol particle size (1-3 microm mass median aerodynamic diameter and geometric standard deviation < 2 microm), and the concentration of this respirable particle fraction produced by an aerosol system may enhance delivery through endotracheal tubes and to the lower respiratory tract in infants and children with low V(T) and low inspiratory rates. Attention to the choice of delivery system and to details of proper MDI technique (shaking, priming, immediate actuation, and avoiding multiple actuations prior to inhalation), choice of the aerosol spacer and patient interface (type of face mask, endotracheal tube, mouthpiece), spacer cleaning, and consideration of the medicine to be aerosolized (solution or suspension, viscosity) permit adjustment of the aerosol regimen to optimize delivery. All the patient-related, system-related, and operator-dependent considerations combined can greatly impact aerosol delivery efficacy and improve therapeutic response. Therefore, education and motivation of medical personnel, parents and caregivers, and patients regarding factors that influence aerosol efficiency and teaching of proper technique must be prioritized in order to improve aerosol delivery. Aerosol therapy to all patients, especially infants and young children, would be well served if we had a clear understanding of the efficiency and functional differences among the various drugs and devices. These are substantive issues with daily therapeutic impact that have received increasingly outspoken concern over the past decade by aerosol scientists and clinicians. These issues must be given due attention by drug and device manufacturers as well as by regulatory agencies. The medication, the device, and the conditions under which they are tested must be considered together and studied as thoroughly as the medications themselves with respect to total output and particle size distribution. As noted by Bisgaard, medication dose recommendations are useless unless the device and technique used are specified. Medication dose recommendation could be facilitated by setting equivalent standards for generic and brand-name medications and devices. In addition, standardization of in vitro models with better replicas of infants' and children's anatomy (oropharynx, upper airways), and better in vitro lung models, plus utilization of realistic breathing patterns of infants and children will improve in vitro prediction of the in vivo dose delivered to lower airways. This would greatly facilitate selection of delivery systems under specific circumstances for infants and children of various ages). Safety profile, therapeutic efficacy, and efficiency of aerosolized medications delivered to infants and children need to be rigorously studied. This is particularly true for medications with potentially great benefit but possible adverse effects, such as inhaled glucocorticoid therapy in extremely premature infants. Common sense, ethics, and due respect for the same high standard of approval requirements of adults and older children should motivate further research in understanding and improving aerosol delivery in infants and young children.

In a randomized trial in 102 preterm newborns with respiratory distress syndrome (RDS) it has been shown that early Ambroxol treatment (30 mg kg(-1) over the first 5 days) significantly reduces the incidence of RDS-associated complications [bronchopulmonary dysplasia (BPD), intraventricular haemorrhage, post-natal acquired pneumonia]. The aim of the present analysis was to investigate the effect of Ambroxol treatment on lung function in newborns who developed BPD. Respiratory function testing (RFT) was performed immediately after extubation and at day 28. Tidal volume (VT) and respiratory frequency (f) were measured during tidal breathing using the deadspace free flow-through technique. The lung mechanic parameter VT/maxPes was determined by measuring the maximal oesophageal pressure changes, maxPes, with a catheter tip pressure transducer. In the placebo group 36/50 infants were extubated within the first 28 days of life and 13/36 (36%) developed BPD. In the Ambroxol group 44/52 were extubated and 9/44 (20%) developed BPD. After extubation, RFT showed (i) no statistically significant difference in the ventilatory parameters of either treatment group, (ii) improved (P<0.05) lung mechanics (VT/maxPes) in Ambroxol group compared to controls (94+/-27 ml kPa(-1) vs. 8.1+/-2.6 ml kPa(-1)) and (iii) no statistically significant difference in lung function between infants with and without BPD. At day 28 we found (i) no effect of early Ambroxol treatment on lung functions, (ii) significantly (P < 0.05) higher f (58.5+/-11.7 min(-1) vs. 49.7+/-10.1 min(-1)) and significantly (P<0.01) lower V(T) (9.6+/-1.9 ml vs. 12.3+/-2.7 ml) and V(T)/maxPes (8.9+/-2.6 ml kPa(-1)] vs. 12.0+/-2.9 ml kPa(-1)) in infants with BPD compared to infants without and (iii) these differences are not influenced by early Ambroxol treatment. If the process of BPD development is induced, early Ambroxol treatment has no influence on impaired lung function at day 28.

Three modes of inhaled therapy are available for the administration of bronchodilators in acute respiratory diseases in children: spacer devices, nebulizers, inhaled powders. Principles, medications available in France, and dosages, are presented. Acute asthma is the main indication.

Over the past decade there has been a significant shift to the use of murine models for investigations into the molecular basis of respiratory diseases, including asthma and chronic obstructive pulmonary disease. These models offer the exciting prospect of dissecting the complex interaction between cytokines, chemokines and growth related peptides in disease pathogenesis. Furthermore, the receptors and the intracellular signalling pathways that are subsequently activated are amenable for study because of the availability of monoclonal antibodies and techniques for targeted gene disruption and gene incorporation for individual mediators, receptors and proteins. However, it is clear that extrapolation from these models to the human condition is not straightforward, as reflected by some recent clinical disappointments. This is not necessarily a problem with the use of mice itself, but results from our continued ignorance of the disease process and how to improve the modelling of complex interactions between different inflammatory mediators that underlie clinical pathology. This review highlights some of the strengths and weaknesses of murine models of respiratory disease.