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PubMed1999

[Asthma in children below 5 years of age: diagnosis and treatment].

Asthma is the most frequent chronic disease in pediatrics and the increase in its prevalence is a major public health problem. Diagnosis may be difficult in the young child, symptomatology most often occurring following a viral infection. It is important not to ignore a foreign body in the airways or fibrocystic disease and asthma remains, particularly in infants, a diagnosis of elimination. Misdiagnosis or insufficient treatment of asthma may risk the development of irreversible histological lesions and also could compromise pulmonary growth and the child's lung reserve. Spacer devices and nebulisers enable inhaled therapy to be administered to very young children. The value of early diagnosis is to institute appropriate treatment notably in severe asthma with inhaled corticosteroid therapy, the aim being to reduce remodelling lesions of the airways. The minimal effective dose should be defined to minimalize side-effects. The treatment of asthma is not restricted to pharmacotherapy: attempts should be made to reduce intercurrent viral infections, domestic pollution (including smoking) and allergenic concentrations. However, as for all chronic diseases, the clinician will encounter poor compliance. The work of education and support of health professionals is fundamental to the management of asthma.

Asthma↗
PubMed2000

[Asthma and the child below 5 years of age: diagnosis and treatment].

Asthma is the most frequent chronic disease in pediatrics and the increase in its prevalence is a major public health problem. Diagnosis may be difficult in the young child, symptomatology most often occurring following a viral infection. It is important not to ignore a foreign body in the airways or fibrocystic disease and asthma remains, particularly in infants, a diagnosis of elimination. Misdiagnosis or insufficient treatment of asthma may risk the development of irreversible histological lesions and also could compromise pulmonary growth and the child's lung reserve. Spacer devices and nebulisers enable inhaled therapy to be administered to very young children. The value of early diagnosis is to institute appropriate treatment notably in severe asthma with inhaled corticosteroid therapy, the aim being to reduce remodelling lesions of the airways. The minimal effective dose should be defined to minimalise side-effects. The treatment of asthma is not restricted to pharmacotherapy: attempts should be made to reduce intercurrent viral infections, domestic pollution (including smoking) and allergenic concentrations. However, as for all chronic diseases, the clinician will encounter poor compliance. The work of education and support of health professionals is fundamental to the management of asthma.

Age Factors↗
PubMed2001

The clinical use of colistin in patients with cystic fibrosis.

Colistin is a cationic polypeptide antibiotic from the polymyxin family that was first introduced in 1962 but abandoned in the early 1970s because of initial reports of severe toxicities. However, a recent increase in the prevalence of multidrug resistant (MDR) Pseudomonas aeruginosa and the lack of novel agents in development calls for a need to re-examine the role of colistin therapy in patients with cystic fibrosis. Current data supports the use of intravenous colistimethate for the treatment of acute pulmonary exacerbations involving MDR P. aeruginosa and inhaled therapy for initial colonization. The frequency of nephrotoxicity and severity of neurotoxicity seem to be substantially less than previously believed. In addition, recent pharmacokinetic and pharmacodynamic data suggests new intravenous dosing regimens may enhance efficacy while minimizing toxicities; such regimens deserve further evaluation. Pre- and post-treatment spirometry is recommended at initiation of inhaled colistin therapy to identify sensitized individuals. Judicious use of colistin where the benefits have been clearly documented will retain this as a useful agent in the management of P. aeruginosa infections in patients with cystic fibrosis.

Anti-Bacterial Agents↗
PubMed2002

A 500-ml plastic bottle: an effective spacer for children with asthma.

Inhaled therapy using a metered-dose inhaler (MDI) with attached spacer has been increasingly recognized as the optimal method for delivering asthma medication for acute attacks and chronic prophylaxis. However, in developing countries the cost and availability of commercially produced spacers limit the use of MDI-spacer delivery systems. A 500-ml plastic bottle has been recently adapted to function as a spacer. This article reviews the current data on the efficacy of this bottle-spacer and discusses its advantages and limitations. It is concluded that a modified 500-ml plastic bottle is an effective spacer; modification and use of this device should be incorporated into international guidelines for the management of children with asthma.

Anti-Asthmatic Agents↗
PubMed1999

Can tobramycin inhalation be improved with a jet nebulizer?

Data on the pharmacokinetics of antibiotics after inhalation are limited. The aim of this pilot study was to assess the pharmacokinetics of tobramycin under optimalized and standardized aerosol circumstances and, furthermore, to be able to consider possible treatment of exacerbations with inhalation therapy. Six patients were studied after inhalation of 600 mg tobramycin. A jet nebulizer loaded with a 10% solution of tobramycin in water was used. The percentage of the dose that was systemically absorbed ranged from 1.0% to 16.6%. The maximum serum levels of tobramycin ranged from 0.77 mg/L to 3.63 mg/L (mean 1.70 +/- 1.01). The pharmacokinetic data were best described by a two-compartment model. Compared to intravenous administration, the long terminal half-life (mean 9.47 h +/- 3.28 h) could be explained by the slow absorption of tobramycin from the site of administration (flip-flop model). Despite standardized aerosol conditions, considerable interpatient variability was observed. However, the relatively low serum levels allow a further increase of the dose.

Administration, Inhalation↗
PubMed1990

[A case of pulmonary nocardiosis associated with middle lobe atelectasis].

Pulmonary nocardiosis is a rare disease. We reported a case of pulmonary nocardiosis associated with middle lobe atelectasis. A 66-year-old female was admitted to Saga Medical School Hospital with complaints of fever, productive cough and hemosputum. Nocardia asteroides was isolated from her sputum and bronchial lavage fluid. Administration of sulfamethoxazole-trimethoprim (ST) improved her symptoms and Nocardia asteroides were rapidly eliminated from her sputum. However, she had severe side effects of ST: toxic dermatitis, granulocytopenia and liver dysfunction, whereupon administration of ST was stopped. About two weeks later, Nocardia asteroides appeared again in her sputum. Either netilmicin (NTL) or minocycline (MINO) given consecutively could not eliminate Nocardia asteroides from her sputa. Subsequently a combination therapy of OFLX administration and gentamicin inhalation was tried. This treatment improved her symptoms and eradicated Nocardia asteroides from her sputa completely. In vitro study, ST, MINO and aminoglycosides showed good susceptibility against Nocardia asteroides. In this case, it was revealed that GM inhalation therapy is also very useful for pulmonary Nocardiosis.

Aged↗
PubMed2002

Pulmonary drug delivery systems: recent developments and prospects.

Targeting drug delivery into the lungs has become one of the most important aspects of systemic or local drug delivery systems. Consequently, in the last few years, techniques and new drug delivery devices intended to deliver drugs into the lungs have been widely developed. Currently, the main drug targeting regimens include direct application of a drug into the lungs, mostly by inhalation therapy using either pressurized metered dose inhalers (pMDI) or dry powder inhalers (DPI). Intratracheal administration is commonly used as a first approach in lung drug delivery in vivo. To convey a sufficient dose of drug to the lungs, suitable drug carriers are required. These can be either solid, liquid, or gaseous excipients. Liposomes, nano- and microparticles, cyclodextrins, microemulsions, micelles, suspensions, or solutions are all examples of this type of pharmaceutical carrier that have been successfully used to target drugs into the lungs. The use of microreservoir-type systems offers clear advantages, such as high loading capacity and the possibility of controlling size and permeability, and thus of controlling the release kinetics of the drugs from the carrier systems. These systems make it possible to use relatively small numbers of vector molecules to deliver substantial amounts of a drug to the target. This review discusses the drug carriers administered or intended to be administered into the lungs. The transition to CFC-free inhalers and drug delivery systems formulated with new propellants are also discussed. Finally, in addition to the various advances made in the field of pulmonary-route administration, we describe new systems based on perfluorooctyl bromide, which guarantee oxygen delivery in the event of respiratory distress and drug delivery into the lungs.

Administration, Inhalation↗
PubMed2001

[Japanese guideline for treatment and management of childhood asthma and its originality].

Japanese guideline for treatment and management of childhood asthma was published in April, 2000. This is the Japan original guideline. The general and practical asthma treatment in Japan is described. We compared with this guideline and GINA. There is not a difference in the diagnosis and concept of bronchial asthma. This guideline for several Japan original therapies are described. The originality of this guideline is the early use of theophylline. There is not the entry of the use of oral steroid. There are many Japan original therapies such as the isoproterenol continuous inhalation therapy. Also, as for this guideline the education, vaccination and exercise of the patient are written in detail. We hope that this guideline is translated to English and be published.

Adolescent↗
PubMed1992

[Evaluation of aerosol therapy of streptomycin for tracheobronchial and pulmonary tuberculosis].

The clinical features of tracheobronchial tuberculosis are distinct from those of pulmonary tuberculosis in some aspects. Streptomycin (SM) is claimed by some investigators that it has a tendency to promote the development of bronchial stenosis due to scarred healing of the involved endobronchial mucosa, and, for that reason, they recommend not to use it in treatment of bronchial tuberculosis. In some patients with pulmonary tuberculosis, who have renal or hearing disturbance, SM avoided. Yet unless SM is used improvement of tuberculosis could be delayed. It is the purpose of the present investigation to point out that aerosol therapy of SM is useful for patients with respiratory tuberculosis. Furthermore, we wish to demonstrate that we can safely treat the patients with respiratory tuberculosis who suffer from renal function or hearing disorder by use of aerosol therapy of SM. Prior to clinical application of the inhalation therapy, we confirmed that the therapy was not harmful. Serum concentration of SM, when inhaled, was measured in 9 volunteers. Before and after administration of SM aerosol, spirograms were examined in 4 volunteers, nevertheless, no special abnormality was recognized. It seemed that serum concentration of SM after the administration was two low to evoke adverse reactions (less than 3.0 gamma). In 6 patients with pulmonary tuberculosis, blood gases were measured and no obvious change was observed. As a result, it was demonstrated that the endobronchial tuberculous lesions improved faster when treated by inhalation of aerosolized SM as compared with the conventional injection therapy, without evoking any apparent adverse reactions. In some of the patients with pulmonary tuberculosis, it seemed that the therapy was useful.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1981

Comparison of inhaled and intravenous terbutaline in acute severe asthma.

In patients with acute severe asthma, 5 mg of terbutaline by inhalation and 500 microgram intravenously in divided doses both produced equally effective but not maximal bronchodilatation. There was no difference in the production of side-effects. These results support the view that inhaled therapy can be as effective in patients with acute severe asthma as injected treatment. In view of the risks of intravenous treatment, especially using high doses, inhaled bronchodilator therapy would seem advisable as initial treatment.

Acute Disease↗
PubMed2001

Influence of inhaled steroids on pulmonary epithelial permeability to Tc99m-dTPA in atopic asthmatic children.

The lung permeability of asthmatic children has been reported to be similar, lower, or higher than that of healthy subjects. The aim of this study was to clarify these discrepancies and also assess the effect of inhaled steroids on lung permeability. Tc99m-diethylenetriaminepentaaceticacid (Tc99m-DTPA) clearance in children with mild unstable asthma (n = 13; mean age 9.3 +/- 0.7 years) was compared with that of a group of healthy subjects (n = 11; mean age 8.9 +/- 0.8 years). Symptom scores, forced-expiratory volume in the first second (FEV1), and peak expiratory flow rate variability (PEFR-v) of asthmatics were recorded and an inhaled steroid (budesonid) was recommended after first scintigraphic evaluation for 8 weeks. Two consecutive scintigraphic studies were performed before and after treatment. Symptoms, FEV1, and PEFR-v significantly improved throughout the study. Baseline DTPA clearance rate in the asthmatics was significantly higher from that of control group (1.3 +/- 0.2 and 0.7 +/- 0.1%/min, respectively) (p < 0.05). DTPA clearance rate of asthmatics significantly increased to 1.7 +/- 0.3%/min at end of inhaled therapy (p < 0.05). Our data show that DTPA clearance in unstable asthmatic children is significantly higher than that found in healthy subjects, and that a higher rate was obtained following inhaled steroid therapy. Thus, the clinical significance of these observations needs further studies to test whether DTPA clearance index is a valid tool for monitoring asthmatic children and to explore the mechanisms involved in radioaerosol clearance rates in pediatric asthma.

Administration, Inhalation↗
PubMed1999

Reduction in health care resource utilization associated with extended-release theophylline.

BACKGROUND: People with airway disease are high utilizers of health care resources. Few studies document the value of alternative therapies in reducing utilization. Studies examining theophylline, which demonstrate reduction in resource utilization, have been primarily of short duration in hospitalized settings with small samples. OBJECTIVE: The purpose of this study was to examine the role of oral extended-release theophylline in reducing health care utilization over an extended period of time when added to existing inhaler therapy for ambulatory patients with airway disease. METHODS: We used a retrospective, pretest/posttest design in examining the 1990-1993 South Carolina Medicaid database to compare health care utilization of 455 ambulatory patients for 4 months before and 6 months after extended-release theophylline was added to their treatment regimen. We assessed the following three outcomes: inhaler use, physician office visits, and emergency department visits, all measured in units/person/month. RESULTS: Our sample consisted of patients taking beta2-agonist only (n = 393), steroid only (n = 25), and beta2-agonist plus steroid (n = 37). Inhaler use and physician office visits declined significantly among beta2-agonist users, as well as within the entire sample. Initiation of extended-release theophylline therapy was associated with a 30% decline in utilization of inhaler and physician office visits, influenced mostly by the decline with the beta2-agonist group. CONCLUSION: The results of this effectiveness study using an administrative claims database are consistent with the published randomized clinical trials that document the value of extended-release theophylline when added to existing inhaler therapy.

Administration, Inhalation↗
PubMed1989

[Adequate respiratory therapy in polytrauma in the prehospital phase by pulse oximetry monitoring].

As a result of recent medical development, the pulse oximetry enables the emergency-doctor to carry out an objective and continuous respiratory monitoring. In a prospective study we showed the consequences of this new procedure for prehospital respiratory therapy and the following posttraumatic development of polytraumatized patients. In 1988 within 6 months we carried out a continuous monitoring of 13 severely polytraumatized patients in the prehospital period using the pulse oximeter Nellcor N-10 and Pulsat. In order to see the posttraumatic respiratory complications, we studied the respiratory therapy of the following 3 days as well as the course of disease until the patients' release of the hospital. 38% of the patients were intubated immediately after the accident and further 12% before arriving at the hospital. The oxygen inhalation therapy of 63% spontaneously breathing patients and the mechanical ventilation patterns of 80% of the ventilated patients were modified in the prehospital period, because 60% of the patients with standard mechanical ventilation showed hypoxygenations. During the first 3 posttraumatic days 23% of the patients died the the number of mechanical ventilated patients increased from 46% to 54% because of surgical interventions. A respiratory therapy of more than 3 days was applied on 40% of the surviving patients, with 20% receiving mechanical ventilation. Thereby no primarily respiratory complications could be seen. While not being decisive for immediate intubation, monitoring with a pulse oximeter used by the emergency-doctor plays an essential part in carrying out an effective control and dosage of the therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMedDate not supplied

Echocardiographic evidence of improved hemodynamics during inhaled nitric oxide therapy for persistent pulmonary hypertension of the newborn.

To evaluate the cardiovascular effects of inhaled nitric oxide (NO) on the systemic and pulmonary circulations, 25 consecutive infants with severe persistent pulmonary hypertension of the newborn (PPHN) underwent serial echocardiographic evaluations before and during inhaled NO therapy. Estimation of the systolic pulmonary artery pressure (SPAP) was derived from measurement of a tricuspid regurgitant jet using Bernoulli's equation. We also derived a pulmonary/systemic pressure ratio to evaluate overall cardiopulmonary effects. Paired measurements of estimated SPAP decreased from 62.0 +/- 3.8 mmHg to 44.7 +/- 4.3 mmHg (p < 0.01) during inhaled NO therapy. The pulmonary/systemic pressure ratio decreased from 0.98 +/- 0.06 to 0.59 +/- 0.04 during NO therapy (p < 0.01), indicating a significant decline in the vascular resistance between the two circulations. These changes also correlated with changes in the extrapulmonary shunt patterns at the ductus arteriosus and foramen ovale seen during inhaled NO therapy. The decreased right-to-left shunting was accompanied by a parallel (64%) improvement in systemic oxygenation, with the alveolar-arterial oxygen gradient (A-a DO2) falling from 591 +/- 14 mmHg to 380 +/- 33 mmHg (p < 0.01). We found echocardiography to be a useful clinical tool for evaluating and monitoring pulmonary artery pressure in infants with PPHN. Measurement of the SPAP and the pulmonary/systemic pressure ratio gave a quantitative estimation of the severity of PPHN, and the extrapulmonary shunt flow patterns at the ductus arteriosus and foramen ovale gave qualitative estimates of its severity. Inhaled NO increased pulmonary blood flow and oxygenation and improved the systemic cardiopulmonary hemodynamics in this group of infants.

Administration, Inhalation↗
PubMed1996

A theoretic analysis of the effect of pulmonary vasodilation on pulmonary venous pressure: implications for inhaled nitric oxide therapy.

BACKGROUND: Although the use of inhaled nitric oxide offers certain advantages over more traditional pulmonary vasodilators, concerns have emerged because of reports of acute pulmonary edema during nitric oxide administration in patients with chronic heart failure. It is unclear whether the pulmonary vasodilating action of nitric oxide could, by itself, cause venous pressures to rise in the lung and why patients with preexisting chronic heart failure are at greatest risk for the development of pulmonary edema during inhaled nitric oxide therapy. METHODS: The cardiovascular system was modeled as time-varying elastances; the pulmonary and systemic vascular systems were each modeled as a series of resistive and compliance elements. Protocols were devised to examine the effects of a decrease in pulmonary vascular resistance on pulmonary venous pressure under different conditions of contractile state and volume status. RESULTS: Under all conditions studied, pulmonary venous pressure increased as pulmonary vascular resistance decreased. Increases in pulmonary venous pressure were caused by volume shifts between pulmonary arterial and venous compartments. These volume shifts were accentuated by high volume status. The impact of alterations in contractile state was minimal. CONCLUSIONS: Pulmonary vasodilation by itself can lead to an increase in pulmonary venous pressure that is mediated by shifts of blood between arterial and venous compartments of the pulmonary bed. Furthermore, impairment in ventricular contractile state by itself has relatively little effect on pulmonary venous pressure. The magnitude of the increase in pulmonary venous pressure is largely determined by the volume status and the initial value of pulmonary vascular resistance.

Administration, Inhalation↗
PubMed1990

[Comparison of the effect of 2 therapy concepts in the treatment of Pneumocystis carinii pneumonia. Cotrimoxazole for 21 days versus sequential therapy with cotrimoxazole followed by pentamidine inhalation].

Standard therapy of pneumocystis carinii pneumonia with cotrimoxazole and intravenous pentamidine second line therapy both have a response rate of 75 to 90%. As severe side effects, myelotoxicity and skin reaction have been observed which may occur from treatment day 7 on. In order to prevent such side effects as well as reduce hospitalization times, an open, randomized pilot study was designed. Object of this study was the comparison of efficacy and safety of two different treatment schemes: standard therapy versus sequential treatment. Twelve patients were treated according to study design: five patients with cotrimoxazole only, and seven patients with sequential therapy consisting of cotrimoxazole followed by pentamidine aerosol. All patients were treated for 21 days. Four out of five patients with cotrimoxazole, and two out of seven patients with sequential therapy, were successfully treated and had no pneumocystis carinii pneumonia relapses within four weeks after termination of treatment. Each group had one treatment failure. Four patients under sequential treatment were not evaluable. - In spite of the rather unfavourable preliminary results, the study should be continued. However, patients with secondary opportunistic infections respectively other severe diseases should not be included into the study.

Administration, Inhalation↗
PubMed1998

Asthma in pregnant patients: pathophysiology and management.

Epidemiological studies have shown that approximately 1-4% of pregnancies are complicated by bronchial asthma, but these percentages are likely to be substantially underestimated because, in many cases, the condition will be undiagnosed, just as in the nonpregnant population. Undertreatment of pregnant asthmatics especially owing to unfounded fears of adverse pharmacological effects on the developing foetus, remains the major problem. Several studies have demonstrated that severe, uncontrolled asthma may produce serious maternal and foetal complications; consequently pregnant females with severe asthma must be considered at a particularly high risk. In this review we present recent data regarding the physiological respiratory changes in pregnancy, the effect of asthma on the course and outcome of pregnancy, the effect of the pregnancy on the course of the illness and options for effective and appropriate medical management with emphasis for preventive and pharmacological aspects. Since bronchial asthma is a chronic condition with acute exacerbations, a continuing management is necessary to control symptoms, prevent acute obstructions and reduce the degree of airway inflammation. An optimized management of asthma in pregnant females is supported by four integral components: 1)objective assessment of maternal lung function and foetal wellbeing 2) avoidance or control of environmental precipitating factors; 3) pharmacological therapy; and 4) patient education. As regards to pharmacological therapy, we must state that patients with poorly controlled asthma must be evaluated for the use of the same drugs and protocols utilized for nonpregnant females in order to avoid the risk of a potentially life-threatening evolution of the disease. Inhalation therapy is generally better than systemic treatment; in fact this route of drug delivery strongly reduces the risk of systemic side effects and the likelihood of foetal penetration.

Animals↗
PubMed2001

COPD: management of acute exacerbations and chronic stable disease.

Acute exacerbations of chronic obstructive pulmonary disease (COPD) are treated with oxygen (in hypoxemic patients), inhaled beta2 agonists, inhaled anticholinergics, antibiotics and systemic corticosteroids. Methylxanthine therapy may be considered in patients who do not respond to other bronchodilators. Antibiotic therapy is directed at the most common pathogens, including Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis. Mild to moderate exacerbations of COPD are usually treated with older broad-spectrum antibiotics such as doxycycline, trimethoprim-sulfamethoxazole and amoxicillin-clavulanate potassium. Treatment with augmented penicillins, fluoroquinolones, third-generation cephalosporins or aminoglycosides may be considered in patients with more severe exacerbations. The management of chronic stable COPD always includes smoking cessation and oxygen therapy. Inhaled beta2 agonists, inhaled anticholinergics and systemic corticosteroids provide short-term benefits in patients with chronic stable disease. Inhaled corticosteroids decrease airway reactivity and reduce the use of health care services for management of respiratory symptoms. Preventing acute exacerbations helps to reduce long-term complications. Long-term oxygen therapy, regular monitoring of pulmonary function and referral for pulmonary rehabilitation are often indicated. Influenza and pneumococcal vaccines should be given. Patients who do not respond to standard therapies may benefit from surgery.

Acute Disease↗