[Guideline for the Diagnosis and Treatment of Asthma - Addendum 2020 - Guideline of the German Respiratory Society and the German Atemwegsliga in Cooperation with the Paediatric Respiratory Society and the Austrian Society of Pneumology]. / S2k-Leitlinie zur Diagnostik und Therapie von Patienten mit Asthma ­ Addendum 2020.

The present addendum of the guideline for the diagnosis and treatment of asthma (2017) complements new insights into the diagnosis and management of asthma as well as for the newly approved drugs for the treatment of asthma. Current, evidence-based recommendations on diagnostic and therapeutic approaches are presented for children and adolescents as well as for adults with asthma.

[Guideline for the Diagnosis and Treatment of Asthma - Guideline of the German Respiratory Society and the German Atemwegsliga in Cooperation with the Paediatric Respiratory Society and the Austrian Society of Pneumology]. / S2k-Leitlinie zur Diagnostik und Therapie von Patienten mit Asthma.

The present guideline is a new version and an update of the guideline for the diagnosis and treatment of asthma, which replaces the previous version for german speaking countries from the year 2006. The wealth of new data on the pathophysiology and the phenotypes of asthma, and the expanded spectrum of diagnostic and therapeutic options necessitated a new version and an update. This guideline presents the current, evidence-based recommendations for the diagnosis and treatment of asthma, for children and adolescents as well as for adults with asthma.

Exhaled nitric oxide in symptomatic children at preschool age predicts later asthma.

BACKGROUND: Prediction of asthma in young children with respiratory symptoms is hampered by the lack of objective measures applicable in clinical routine. In this prospective study in a preschool children cohort, we assessed whether the fraction of exhaled nitric oxide (FeNO), a biomarker of airway inflammation, is associated with asthma at school age. METHODS: At baseline, IgE and eosinophils were measured in the blood, and FeNO was measured offline in 391 children aged 3-47 months with lower airway symptoms. We developed an asthma predictive index (API) including high FeNO as major criterion. At follow-up, primary outcome was physician-diagnosed asthma based on standardized interviews in those children reaching school age (n = 166). RESULTS: FeNO was significantly elevated in those children with later asthma (68/166) as compared to children not developing asthma. Median (IQR) FeNO was 10.5 (6.6-17.2) vs. 7.4 (5.3-10.3) ppb. Per 5 ppb FeNO increase, the odds ratio (95% CI) for asthma increased by 2.44 (1.61-3.70) without changing when adjusting for confounders. Using the new API, children scored at risk had 58.0% probability for later asthma, whereas the negative predictive value was 78.2%, which was comparable to the classical API. CONCLUSIONS: In this cohort of high-risk preschool children, elevated FeNO is associated with increased risk for school-age asthma. The new API including FeNO identifies children at risk of later asthma comparably to the classical API, but does not require blood sampling.

Parent misperception of control in childhood/adolescent asthma: the Room to Breathe survey.

The aim of our study was to determine how often asthma control is achieved in children and adolescents, and how asthma affects parents' and children's daily lives. Interviews, including the childhood asthma control test (C-ACT), were conducted with 1,284 parents of asthmatic children (aged 4-15 yrs), as well as with the children themselves (aged 8-15 yrs; n=943), in Canada, Greece, Hungary, the Netherlands, South Africa and the UK. Parents reported mild asthma attacks at least weekly in 11% of children, and serious attacks (requiring oral corticosteroids or hospitalisation) at least annually in 35%. Although 73% of parents described their child's asthma as mild or intermittent, 40% of children/adolescents had C-ACT scores ≤ 19, indicating inadequate control, and only 14.7% achieved complete Global Initiative for Asthma (GINA)-defined control and just 9.2% achieved Scottish Intercollegiate Guidelines Network (SIGN)/British Thoracic Society (BTS)-defined control. Guideline-defined asthma control was significantly less common than well-controlled asthma using the C-ACT (p<0.001). Asthma restricted the child's activities in 39% of families and caused lifestyle changes in 70%. Complete asthma control is uncommon in children worldwide. Guideline-defined control measures appear to be more stringent than those defined by C-ACT or families. Overall, parents underestimate their child's asthma severity and overestimate asthma control. This is a major potential barrier to successful asthma treatment in children.

Plasma phospholipase A2 activity in patients with asthma: association with body mass index and cholesterol concentration.

BACKGROUND: Secretory phospholipases A2 (sPLA2) have functions relevant to asthmatic inflammation, including eicosanoid synthesis and effects on dendritic cells and T cells. The aim of this study was to measure sPLA2 activity in patients with stable and acute asthma and to assess potential associations with body mass index (BMI), and plasma cholesterol and vitamin C concentrations. METHODS: Plasma sPLA2 activity and concentrations of cholesterol and vitamin C were measured in 23 control subjects and 61 subjects with stable asthma (42 mild to moderate, 19 severe). In addition, sPLA2 activity was measured in 36 patients experiencing acute asthma and in 22 of these patients after recovery from the acute attack. RESULTS: sPLA2 activity was not significantly greater in severe (499.9 U; 95% confidence interval (CI) 439.4 to 560.4) compared with mild to moderate asthmatic subjects (464.8; 95% CI 425.3 to 504.3) or control subjects (445.7; 95% CI 392.1 to 499.4), although it was higher in patients with acute asthma (581.6; 95% CI 541.2 to 622.0; p<0.001). Male gender, high plasma cholesterol, increased BMI and atopy were associated with increased sPLA2 activity, while plasma vitamin C was inversely correlated with sPLA2 activity in patients with stable asthma and in control subjects. There were significant interactions between gender and plasma cholesterol and between gender and vitamin C in relation to sPLA2 activity. CONCLUSIONS: Plasma sPLA2 may provide a biological link between asthma, inflammation, increased BMI, lipid metabolism and antioxidants. Interactions among these factors may be pertinent to the pathophysiology and increasing prevalence of both asthma and obesity.

Definition, assessment and treatment of wheezing disorders in preschool children: an evidence-based approach.

There is poor agreement on definitions of different phenotypes of preschool wheezing disorders. The present Task Force proposes to use the terms episodic (viral) wheeze to describe children who wheeze intermittently and are well between episodes, and multiple-trigger wheeze for children who wheeze both during and outside discrete episodes. Investigations are only needed when in doubt about the diagnosis. Based on the limited evidence available, inhaled short-acting beta(2)-agonists by metered-dose inhaler/spacer combination are recommended for symptomatic relief. Educating parents regarding causative factors and treatment is useful. Exposure to tobacco smoke should be avoided; allergen avoidance may be considered when sensitisation has been established. Maintenance treatment with inhaled corticosteroids is recommended for multiple-trigger wheeze; benefits are often small. Montelukast is recommended for the treatment of episodic (viral) wheeze and can be started when symptoms of a viral cold develop. Given the large overlap in phenotypes, and the fact that patients can move from one phenotype to another, inhaled corticosteroids and montelukast may be considered on a trial basis in almost any preschool child with recurrent wheeze, but should be discontinued if there is no clear clinical benefit. Large well-designed randomised controlled trials with clear descriptions of patients are needed to improve the present recommendations on the treatment of these common syndromes.

Diagnosis and treatment of asthma in childhood: a PRACTALL consensus report.

Asthma is the leading chronic disease among children in most industrialized countries. However, the evidence base on specific aspects of pediatric asthma, including therapeutic strategies, is limited and no recent international guidelines have focused exclusively on pediatric asthma. As a result, the European Academy of Allergy and Clinical Immunology and the American Academy of Allergy, Asthma and Immunology nominated expert teams to find a consensus to serve as a guideline for clinical practice in Europe as well as in North America. This consensus report recommends strategies that include pharmacological treatment, allergen and trigger avoidance and asthma education. The report is part of the PRACTALL initiative, which is endorsed by both academies.

Longitudinal monitoring of pediatric cystic fibrosis lung disease using nitrite in exhaled breath condensate.

Cystic fibrosis (CF) lung disease is characterized by airway inflammation and airway infection. Nitrites in exhaled breath condensate (EBC-NO(2)(-)) have been shown to be increased in children and adults with CF compared to healthy controls suggesting its use as a measure of airway inflammation. This longitudinal study aimed to evaluate if repeated measurements of EBC-NO(2)(-) are helpful in monitoring CF lung disease activity in children. Thirty-two children with mild CF lung disease (age 10.6 +/- 3.3 years) were recruited in two study centers. Follow-up visits occurred every 3 months over a period of 1 year with a total of five visits. Each visit included a clinical assessment incorporating a modified Shwachman-Kulczycki (SK) score, spirometry, an oropharyngeal swab, or sputum sample for bacterial analysis and an EBC sample analyzed for NO(2)(-) using a spectrophotometric assay. Furthermore at the first and the last visit a chest radiograph was done and scored (Chrispin-Norman (CN) score). There was no correlation of EBC-NO(2)(-) and parameters of spirometry, SK-score, or CN-score. Furthermore, increased EBC-NO(2)(-) levels did not predict subsequent pulmonary exacerbations. We conclude that repeated measurements of EBC-NO(2)(-) are not helpful in the longitudinal monitoring of mild CF lung disease in children.

[The child with dyspnoea]. / Das Kind mit Atemnot.

Acute dyspnoea is one of the most frequent paediatric emergencies in clinical practice. The anatomy of paediatric airways is different from that of adults. This explains the domination of upper airway diseases as causes of acute respiratory insufficiency in small children. The most common causes for acute dyspnoea in this age group represent Croupsyndrom, foreign body aspiration and epiglottitis. A careful history and physical examination usually provides valuable guidance in the evaluation of the child with acute dyspnoea. Prompt recognition and appropriate treatment of imminent respiratory insufficiency are criticalfor excellent prognosis and will minimise the risk of long-term complications.

Salbutamol delivery from a hydrofluoroalkane pressurized metered-dose inhaler in pediatric ventilator circuits: an in vitro study.

STUDY OBJECTIVES: The aim of our study was to determine the in vitro delivery of salbutamol from a pressurized metered-dose inhaler (pMDI) containing hydrofluoroalkane (HFA) propellant through various delivery devices to four models of a pediatric lung. DESIGN: To determine the effect of electrostatic charge, delivery of salbutamol was initially assessed with a multistage liquid impinger (MSLI) through an inline nonchamber device (Baxter MDI Adapter) and a small (Aerochamber MV) and a large (Nebuhaler) inline chamber device. Following this, the delivery was assessed to four lung models appropriate for a child of 70 kg, 50 kg, 15 kg, and 4 kg, with the same three reduced static devices inserted directly into a pediatric ventilator circuit. MEASUREMENTS AND RESULTS: Reduction of electrostatic charge improved small particle delivery through holding chambers to the MSLI by 12 to 14%. In the ventilator model, the mean delivery was between 1.9% and 5.4% for the nonchamber device, between 14.3% and 27.2% for the small holding chamber, and between 7.2% and 25.7% for the large holding chamber. Delivery was the least efficient in the 4-kg model compared to the 70-kg, 50-kg, and 15-kg models. CONCLUSIONS: Salbutamol from an HFA pMDI is delivered efficiently through inline holding chambers with reduced static in pediatric ventilator settings. A large holding chamber has no advantage over a small holding chamber. In addition, salbutamol delivery is more efficient through a holding chamber than through a nonchamber device.

Partitioning of alterations in pulmonary mechanics due to vascular engorgement in piglets.

The aim of our study was to determine the effects of pulmonary vascular engorgement on airways and pulmonary tissues in juvenile animals before and after methacholine (Mch)-induced changes in lung function. Five anesthetized, paralyzed, and thoracotomized piglets were studied before and during pulmonary vascular engorgement, induced by inflating a left atrial balloon catheter and by calculating respiratory mechanics from measurements of airway opening (Pao) and alveolar pressures (PA), respiratory flow (V'), and volume (V) recorded during mechanical ventilation, using the multilinear regression technique. A maximal increase of 15 mmHg in pulmonary artery pressure (Ppa) resulted in a mean increase in total lung elastance (EL) of 28.6% and in total lung resistance (RL) of 14.9%. Mch increased EL by 21.7% and RL by 29.0%. Inflation of the left atrial balloon with an associated increase in Ppa by 15 mmHg in the presence of Mch resulted in an increase in EL by a further 12.4% (to 135.4% of baseline) and in RL by a further 9.0% (to 139.5% of baseline). The change in RL was associated with a qualitatively similar change in both tissue resistance (Vti) and airway resistance (Raw) before and after Mch-induced changes in lung function. We conclude that increasing pulmonary vascular pressures, by increasing left partial pressure, alters lung function in juvenile animals by altering the mechanical properties of both airways and lung tissues. The methods used in the present study allow a direct assessment of the site of action of vascular engorgement in the lungs and provide a useful model for studying this phenomenon further.

Parental attitudes toward infant pulmonary function testing.

Infant pulmonary function tests (PFTs) have proven increasingly popular and useful for clinical and research purposes. Informed consent requires accurate information on side effects. Our aim was to quantify minor side effects from a parental point of view by means of a questionnaire. The parents of 97 infants attending for PFTs were asked to complete a simple questionnaire. Eighty-one parents (84%) returned the questionnaire. Forty-one percent felt that their infants were not troubled by the process of administering the sedative chloral hydrate, whereas 55% suffered mild to moderate distress. In contrast, 94% of infants were not distressed by the actual PFTs. Similarly, 46% of parents were not distressed by the administration of sedative to their infant, with 49% expressing distress to a mild or moderate degree. Although 73% of parents were not distressed by watching their infants undergo the PFTs, 27% were to a mild to moderate degree. Seventy-three percent of infants were untroubled on waking. Seventy percent of infants had a good nights sleep after the PFTs. The vast majority of parents (94%) were happy to recommend that others allow their infants to undergo similar testing. We noted that most problems caused by infant PFTs relate to the administration of the sedative. Most infants awake from the tests not distressed and sleep normally the following night.

Bronchodilator responsiveness testing using raised volume forced expiration in recurrently wheezing infants.

We hypothesized that a new test of infant lung function, less affected by shifts in lung volume, might better detect bronchodilator effects. Using the raised volume forced expiration technique (RVFET), the effect of a bronchodilator on lung function was studied in 22 infants with a history of recurrent wheeze and five healthy infants. Forced expiratory volume in 0.75 s (FEV0.75), forced expiratory vital capacity (FVC), and forced expiratory flow at 75% of FVC (FEF75%) were measured by forcing expiration, using an inflatable jacket from a lung volume set by an inspiratory pressure of 20 cm H2O. A minimum of five measurements were made at baseline and following the administration of 500 microg of salbutamol from a metered dose inhaler via a small volume metal spacer. Changes in lung function in the group of 25 infants who received salbutamol were compared to seven infants who received placebo aerosol. No significant changes occurred in measures of lung function following salbutamol administration when compared to baseline or placebo despite a significant increase in heart rate. A shift in lung volume is unlikely the reason why infants do not demonstrate a change in forced expiration following bronchodilator administration.

High-percentage lung delivery in children from detergent-treated spacers.

Pressurized metered-dose inhalers attached to spacers are now the most common form of delivery of anti-asthma medication in children. However, no reliable data are available of how much drug reaches the lungs in children of different ages. This information is crucial, as it determines the efficacy of therapy. In this study, we present information on the amount of drug reaching the lungs in children from a pressurized metered-dose inhaler attached to a detergent-coated spacer. We studied 18 asthmatic children inhaling radiolabeled salbutamol through detergent treated spacers to minimize electrostatic charge on the spacer wall. Lung deposition was much higher than expected when using detergent-coated spacers. Mean (SD) lung deposition, expressed as a percentage of the total actuated dose (five actuations), was 16.4% (5.5) in younger children inhaling through a small volume spacer, and 28.2% (6.7) and 41.8% (3. 8) in older children inhaling with different breathing patterns through a large volume spacer. These findings have major implications for dosage regimens for inhaled anti-asthma medication in children. Lower doses may be sufficient for adequate drugs delivered through spacers treated for static to achieve a desired clinical response.

Atypical mycobacterial pulmonary disease and bronchial obstruction in HIV-negative children.

Atypical mycobacterial infection in HIV-negative children usually presents with cervical lymphadenopathy. We report on 10 children who are HIV-negative and who presented with pulmonary disease, in whom either culture-proven atypical mycobacterium infection (four), positive avian Mantoux test (five), or lack of response to human tuberculosis treatment (one) had been observed. One case was subsequently diagnosed as chronic granulomatous disease and illustrates that children with atypical mycobacterial pulmonary infection should have their immune status fully investigated. Bronchial obstruction was observed in eight cases, and of these, endobronchial disease was found in six children. The diagnosis of atypical mycobacterial disease is difficult, and a negative avian Mantoux test does not exclude the diagnosis. The availability of clarithromycin and rifabutin has offered new therapeutic options in treating atypical mycobacterial pulmonary infection, but management of these cases can be prolonged and difficult.

Aerosol delivery to wheezy infants: a comparison between a nebulizer and two small volume spacers.

Inhalation therapy for wheezy infants with either a nebulizer or a pressurized metered-dose inhaler (pMDI) through a spacer is common practice. The aim of our study was to compare aerosol delivery to wheezy infants from a nebulizer and from a pMDI via two small volume spacers. Twenty wheezy infants (aged 4-12 months) were recruited. They inhaled salbutamol from a Pari-Baby nebulizer, from a detergent-coated Babyhaler, and from a Nebuchamber in random order. A filter was placed between the inhalation systems and the patients. The amount of salbutamol deposited on the filter was measured using an ultraviolet spectrophotometer and was expressed as a percentage of the total nebulized or actuated doses. The mean total nebulized dose for the Pari-Baby (1030 micrograms) was higher (P < 0.001) than the mean actuated dose from a pMDI for the Babyhaler (374 micrograms) and for the Nebuchamber (378 micrograms). Mean drug deposition on the filter was 40.2% (150 micrograms) of the total actuated dose for the detergent-coated Babyhaler and 40.7% (154 micrograms) of the total actuated dose for the Nebuchamber. There was no significant difference in drug deposition on the filter between the two spacers. Mean drug deposition on the filter was 25.3% (260 micrograms) of the total nebulized dose for the Pari-Baby nebulizer. There was no weight dependence in drug deposition on the filter for the two spacers, but, drug deposition increased with the subject's weight for the nebulizer. We have shown that aerosol delivery to wheezy infants from a pMDI through small volume spacers is effective and that a higher percentage of the total amount of salbutamol is delivered than from a nebulizer. The weight dependence in drug deposition for the nebulizer can be of clinical relevance.