Monitoring asthma in childhood : Lung function, bronchial responsiveness and inflammation

Peer reviewedPublisher PD

New Spirometry Indices for Detecting Mild Airflow Obstruction.

The diagnosis of chronic obstructive pulmonary disease (COPD) relies on demonstration of airflow obstruction. Traditional spirometric indices miss a number of subjects with respiratory symptoms or structural lung disease on imaging. We hypothesized that utilizing all data points on the expiratory spirometry curves to assess their shape will improve detection of mild airflow obstruction and structural lung disease. We analyzed spirometry data of 8307 participants enrolled in the COPDGene study, and derived metrics of airflow obstruction based on the shape on the volume-time (Parameter D), and flow-volume curves (Transition Point and Transition Distance). We tested associations of these parameters with CT measures of lung disease, respiratory morbidity, and mortality using regression analyses. There were significant correlations between FEV1/FVC with Parameter D (r = -0.83; p < 0.001), Transition Point (r = 0.69; p < 0.001), and Transition Distance (r = 0.50; p < 0.001). All metrics had significant associations with emphysema, small airway disease, dyspnea, and respiratory-quality of life (p < 0.001). The highest quartile for Parameter D was independently associated with all-cause mortality (adjusted HR 3.22,95% CI 2.42-4.27; p < 0.001) but a substantial number of participants in the highest quartile were categorized as GOLD 0 and 1 by traditional criteria (1.8% and 33.7%). Parameter D identified an additional 9.5% of participants with mild or non-recognized disease as abnormal with greater burden of structural lung disease compared with controls. The data points on the flow-volume and volume-time curves can be used to derive indices of airflow obstruction that identify additional subjects with disease who are deemed to be normal by traditional criteria

Addition to inhaled corticosteroids of long-acting beta2-agonists versus anti-leukotrienes for chronic asthma

Asthma patients who continue to experience symptoms despite being on regular inhaled corticosteroids (ICS) represent a management challenge. Long-acting beta2-agonists (LABA) or anti-leukotrienes (LTRA) are two treatment options that could be considered as add-on therapy to ICS.ObjectivesWe compared the efficacy and safety profile of adding either daily LABA or LTRA in adults and children with asthma who remain symptomatic on ICS.Search strategyWe searched the Cochrane Airways Group Specialised Register (up to and including March 2010). We consulted reference lists of all included studies and contacted authors and pharmaceutical manufacturers for other published or unpublished studies.Selection criteriaWe included randomised controlled trials (RCTs) conducted in adults or children with recurrent asthma that was treated with ICS and where a fixed dose of a long-acting beta2-agonist or leukotriene agent was added for a minimum of 28 days.Data collection and analysisTwo authors independently assessed the risk of bias of included studies and extracted data. We sought unpublished data and further details of study design, where necessary.Main resultsWe included 17 RCTs (7032 participants), of which 16 recruited adults and adolescents (6850) and one recruited children aged 6 to 17 years (182). Participants demonstrated substantial reversibility to short-acting beta-agonist at baseline. The studies were at a low risk of bias. The risk of exacerbations requiring systemic corticosteroids was lower with the combination of LABA and ICS compared with LTRA and ICS, from 11% to 9% (RR 0.83, 95% CI 0.71 to 0.97; six studies, 5571 adults). The number needed to treat (NNT) with LABA compared to LTRA to prevent one exacerbation over 48 weeks was 38 (95% CI 22 to 244). The choice of LTRA did not significantly affect the results. The effect appeared stronger in the trials using a single device to administer ICS and LABA compared to those using two devices. In the absence of data from the paediatric trial and the clinical homogeneity of studies, we could not perform subgroup analyses. The addition to ICS of LABA compared to LTRA was associated with a statistically greater improvement from baseline in several of the secondary outcomes, including lung function, functional status measures and quality of life. Serious adverse events were more common with LABA than LTRA, although the estimate was imprecise (RR 1.35, 95% CI 1.00 to 1.82), and the NNT to harm for one additional patient to suffer a serious adverse event on LABA over 48 weeks was 78 (95% CI 33 to infinity). The risk of withdrawal for any reason in adults was significantly lower with LABA and ICS compared to LTRA and ICS (RR 0.84, 95% CI 0.74 to 0.96).Authors' conclusionsIn adults with asthma that is inadequately controlled on low doses of inhaled steroids and showing significant reversibility with beta2-agonists, LABA is superior to LTRA in reducing oral steroid treated exacerbations. Differences favouring LABA in lung function, functional status and quality of life scores are generally modest. There is some evidence of increased risk of SAEs with LABA. The findings support the use of a single inhaler for the delivery of LABA and inhaled corticosteroids. We are unable to draw conclusions about which treatment is better as add-on therapy for children.PLAIN LANGUAGE SUMMARYWhat are the effects of long-acting beta2-agonists compared with anti-leukotrienes when added to inhaled steroids?People who continue to experience asthma symptoms despite regularly taking inhaled corticosteroids are a challenge for management. It is not clear whether the addition of a long-acting beta2-agonist (LABA) such as formoterol or salmeterol would provide more benefit in comparison with an oral anti-leukotriene agent (LTRA), for example zafirlukast or montelukast.Seventeen trials (16 in adults and one in children) were included in this review and were of good quality. We found that the addition of a LABA provides significantly greater protection against exacerbations requiring oral steroids when compared with a LTRA for adults. Based on the results of our analyses, approximately 38 adults (with a range of between 22 and 244) would need to be treated with a LABA rather than a LTRA for 48 weeks to prevent one experiencing an exacerbation needing a course of oral steroids. The trial on children did not contribute data on the main outcome and therefore we could not draw any conclusions for children.LABAs also led to a greater improvement in lung function, improvement in symptoms, use of rescue medication, quality of life and symptoms compared to the use of LTRAs. The magnitude of the improvements was modest. Serious adverse events were more frequent with LABA than with LTRAs although this result was imprecise. Based on our analyses, around 78 people would need to be treated for 48 weeks with a LABA rather than a LTRA for one of them to experience a serious adverse event. However, due to the lack of precision around our result, the true number could be between 33 and infinity. There are currently insufficient data to draw any conclusions about the effects of these drugs in children

Techniques of assessing small airways dysfunction

The small airways are defined as those less than 2 mm in diameter. They are a major site of pathology in many lung diseases, not least chronic obstructive pulmonary disease (COPD) and asthma. The small airways are frequently involved early in the course of these diseases, with significant pathology demonstrable often before the onset of symptoms or changes in spirometry and imaging. Despite their importance, they have proven relatively difficult to study. This is in part due to their relative inaccessibility to biopsy and their small size which makes their imaging difficult. Traditional lung function tests may only become abnormal once there is a significant burden of disease within them. This has led to the term ‘the quiet zone’ of the lung. In recent years, more specialised tests have been developed which may detect these changes earlier, perhaps offering the possibility of earlier diagnosis and intervention. These tests are now moving from the realms of clinical research laboratories into routine clinical practice and are increasingly useful in the diagnosis and monitoring of respiratory diseases. This article gives an overview of small airways physiology and some of the routine and more advanced tests of airway function

Evaluation of Functional Condition of Respiratory Muscles of Patients with a Complicated Bronchial Asthma Pathology and Chronic Obstructive Pulmonary Diseases

The aim of the research was to study the functional state of respiratory muscles and neuro-respiratory drive in patients with a combined pathology of bronchial asthma and chronic obstructive pulmonary disease.The functional condition of the respiratory muscles and the tone of the respiratory centre were determined with the help of a device for occlusion spirometry. Also, the patient was observed with a spirometry, a general plethysmography of the body.Materials and methods.140 patients with combined broncho-obstructive pathology, 34 patients with asthma and 17 patients with COPD were examined. Spirometry, general plethysmography of the body and occlusion spirometry were provided for all patients.Results show a decrease in muscle strength of breath in all categories of patients with broncho-obstructive diseases, especially expressed in patients with bronchial asthma and asthma-COPD intersection. The muscle strength of breath was maintained with a significant increase in COPD patients compared with those with bronchial asthma. With increasing broncho-obstruction in patients with asthma-COPD intersection, there was a progressive and reliable decrease in muscle strength for breath and expiration, as well as a tendency to increase neuron respiratory drive. In patients with asthma-COPD intersection with more expressed symptoms revealed a significant and reliable weakening of muscle strength for breath and increased neuro-respiratory drive. During the work were obtained reliable links of the parameters of respiratory muscle strength not only with the parameters of pulmonary volume and bronchial patency, but also with the degree of neutrophilic inflammation in this category of patients.Conclusions The obtained data on failure of the functional state of the respiratory muscles and the neuro-respiratory drive can be used in the development of rehabilitation programs for the management of patients with combined broncho-obstructive pathology

Performance of a word labeled visual analog scale in determining the degree of dyspnea during exercise-induced bronchoconstriction in children and adolescents with asthma

OBJECTIVE: There is an indirect relationship between airway obstruction in asthma and the intensity of breathlessness (dyspnea). A word labeled visual analog dyspnea scale with a 0-3 score has been widely used for the assessment of the degree of bronchoconstriction, although the perception of such obstruction varies considerably. The objective of this study was to determine whether children and adolescents are able to perceive acute exercise-induced bronchoconstriction (EIB), as well as to measure the discriminatory power of a word labeled visual analog dyspnea scale in relation to the intensity of the EIB. METHODS: A cross-sectional study involving 134 children and adolescents with asthma and submitted to a six-minute steady-state exercise test on a cycle ergometer. The intensity of dyspnea was determined using a word labeled visual analog dyspnea scale prior to each determination of FEV1. The scale is scored from 0 to 3, with a logical sequence of pictures, ranging from no symptoms to severe dyspnea. Variables were determined at baseline, as well as at 5, 10, and 20 min after the exercise test. The accuracy of the dyspnea scale in identifying the degree of EIB was determined by means of ROC curves for the post-exercise fall in FEV1, using cut-off points of 10%, 20%, 30%, and 40%. RESULTS: Of the patients selected, 111 finished the study, and 52 (46.8%) presented with EIB. The area under the ROC curve increased in direct proportion to increases in the degree of bronchoconstriction. CONCLUSIONS: Among children and adolescents with asthma, the accuracy of this dyspnea scale improves as the post-exercise percentage fall in FEV1 increases. However, the predictive value of the scale is suboptimal when the percentage fall in FEV1 is lower.OBJETIVO: Existe uma relação indireta entre a obstrução das vias aéreas em asma e a intensidade de falta de ar (dispneia). Uma escala visual analógica legendada de dispneia com escore de 0-3 pontos tem sido amplamente utilizada na avaliação da broncoconstrição, embora a percepção de tal obstrução seja muito variável. O objetivo deste estudo foi determinar se crianças e adolescentes são capazes de perceber a broncoconstrição aguda induzida por exercício (BAIE), bem como medir o poder discriminatório de uma escala visual analógica legendada de dispneia em relação à intensidade de BAIE. MÉTODOS: Estudo transversal com 134 crianças e adolescentes asmáticos que foram submetidos a um teste de broncoespasmo induzido por seis minutos de exercício em um cicloergômetro. A intensidade da dispneia foi determinada utilizando-se uma escala visual analógica legendada de dispneia antes de cada determinação de VEF1. A escala tem um escore de 0-3 pontos, com desenhos em uma sequência lógica variando entre sem sintomas e dispneia grave. As variáveis foram determinadas no momento basal, assim como em 5, 10 e 20 minutos após o término do teste de exercício. A acurácia da escala de dispneia em detectar o grau de BAIE foi determinada através de curvas ROC para a queda de VEF1 após o exercício, usando pontos de corte de 10%, 20%, 30% e 40%. RESULTADOS: Dos pacientes selecionados, 111 completaram o estudo, e 52 (46,8%) apresentaram BAIE. A área sob a curva ROC progressivamente aumentou com o aumento do grau de broncoconstrição. CONCLUSÕES: Em crianças e adolescentes asmáticos, a acurácia desta escala de dispneia melhora com o aumento do percentual de queda em VEF1 após o exercício. Entretanto, o valor preditivo da escala é subótimo quando a porcentagem de queda em VEF1é menor.Universidade Federal de São Paulo (UNIFESP) Departamento de MedicinaHospital Darcy VargasUNIFESP, Depto. de MedicinaSciEL

Inhaled corticosteroids and growth of airway function in asthmatic children

Airway inflammation and remodelling play an important role in the pathophysiology of asthma. Remodelling may affect childhood lung function, and this process may be reversed by anti-inflammatory treatment. The current study assessed longitudinally whether asthma affects growth of airway function relative to airspaces, and if so whether this is redressed by inhaled corticosteroids (ICS). Every 4 months for up to 3 yrs, lung function was assessed in 54 asthmatic children (initial age 7-16 yrs), who inhaled 0.2 mg salbutamol t.i.d. and 0.2 mg budesonide t.i.d. (beta2-agonist (BA)+ICS), or placebo (PL) t.i.d. (BA+PL) in a randomised, double-blind design. Measurements were carried out before and after maximal bronchodilation. Airway growth was assessed from the change of forced expiratory volume in one second and of maximal expiratory flows (at 60% and 40% of total lung capacity (TLC) remaining in the lung) relative to TLC, as measures of more central, intermediate and more peripheral airways. Growth patterns were compared with the longitudinal findings in 376 healthy children. Airway patency after maximal bronchodilation in patients on BA+PL remained reduced compared to healthy subjects, whereas in patients on BA+ICS a marked improvement was observed to subnormal. No differences between patients and controls could be demonstrated for growth patterns of central and intermediate airway function. Compliance with BA+ICS was 75% of the prescribed dose, resulting in significant, sustained improvement of symptoms and postbronchodilator calibre of central and intermediate airways to subnormal within 2 months, but postbronchodilator small airway patency remained reduced, though improved compared to patients on BA+PL. Anti-inflammatory treatment of asthmatic children is associated with normal functional development of central and intermediate airways. The persistently reduced postbronchodilator patency of peripheral airways may reflect remodelling, or insufficient anti-inflammatory treatment

What can we learn about COPD from impulse oscillometry?

Impulse oscillometry (IOS) is the most commonly used type of forced oscillation technique in clinical practice, although relatively little is known about its application in COPD. Resistance at 20 Hz (R20) is unrelated to COPD severity and does not improve with bronchodilatation or bronchoconstriction, inferring a lack of large airway involvement in COPD. Peripheral airway resistance expressed as frequency dependent heterogeneity between 5 Hz and 20 Hz (R5-R20), and peripheral airway compliance as area under the reactance curve (AX), are both closely related to COPD severity and exacerbations. Both R5-R20 and AX markedly improve in response to long acting bronchodilators, while AX appears to be more sensitive than R5-R20 in response to bronchoconstriction. Future studies may be directed to assess if IOS in combination with spirometry is more sensitive at predicting future exacerbations. Perhaps AX might also be useful as a screening tool in early stage disease or to monitor long term decline in COPD.</p