Do current treatment protocols adequately prevent airway remodeling in children with mild intermittent asthma?

SummaryBackgroundAsthma treatment per Global Initiative for Asthma (GINA) guidelines targets airway remodeling and achievement of normal lung function.ObjectiveTo study inhaled steroid therapy on airway remodeling and achievement of normal lung function.Subjects and set upAsthmatic patients were followed over 5 years .The children were divided into two groups. Group I (148 children-treated group) consisted of all the children using inhaled steroids on a regular basis and group II (50 children-untreated group) included patients with mild intermittent asthma who did not use inhaled steroids and were treated with bronchodilators as needed. Detailed medication and compliance history were recorded and the children underwent regular pre- and post-bronchodilator spirometry and physician examination.ResultsThe incidence of airways remodeling as defined by the low FEV1/FVC post-bronchodilator was markedly increased over the 5-year period in the untreated group compared to the treated group. In the treated group the FEV1/FVC ratio post-bronchodilator decreased from 35% to 20.9% (P<0.009%) compared with the untreated group where the number of children with low FEV1/FVC post-bronchodilator increased from 10% to 28% by the end of the study period.ConclusionPatients with mild asthma who do not receive regular inhaled steroids are at increased risk for airway remodeling. Therefore, we recommend that children with mild intermittent asthma undergo regular pulmonary function testing and that if any deterioration is detected in the FEV1/FVC ratio post-bronchodilators; preventative inhaled corticosteroid therapy be initiated

Systemic Steroid Treatment for Severe Expanding Pneumococcal Pneumonia

The treatment of bacterial community-acquired pneumonia (CAP) is based on appropriate antibiotic therapy and supportive care such as intravenous fluids and supplemental oxygen. There is no available data regarding the use of steroids in CAP in children. We present an unusual case of a child with severe respiratory distress, on the brink of mechanical ventilation, due to a rapidly expanding pneumococcal pneumonia. The administration of systemic steroids resulted in a dramatic response with rapid improvement of clinical and radiological abnormalities followed by improvement of laboratory abnormalities. This case report should raise the awareness of the potential benefits of steroids in the treatment of severe pneumonia in children. Prospective randomized trials are needed to confirm the efficacy of steroids in this setting and to determine which patients would benefit most from this

Patients with cystic fibrosis and normoglycemia exhibit diabetic glucose tolerance during pulmonary exacerbation

AbstractBackgroundPatients with cystic fibrosis and normoglycemia (CF-NGT) have higher but still “normal” glucose levels in the Oral Glucose Tolerance Test (OGTT). Respiratory exacerbation is associated with metabolic stress. The objective of this study was to assess the glucose metabolism and its relation to the steady state pulmonary function (FEV1) in patients with CF-NGT, specifically during pulmonary exacerbations (PE).MethodsCF-NGT patients who were not on steroids, underwent OGTT and intravenous glucose tolerance tests (IVGTT) during PE and 4weeks after complete recovery.ResultsOf the ten recruited patients two had diabetic OGTT and were excluded. The remaining normoglycemic patients displayed during PE a diabetic glucose tolerance with mean glucose levels of 233±8 and 262±11mg/dl at 90 and 120min respectively, compared with normal levels of 154±21and 126±20mg/dl (p<0.002) during the steady state. IVGTT showed a tendency to higher first phase insulin release during PE compared with the steady state.(min 3; 305±80 vs. 216±40pmol\l p=0.075). Finally, when relating the diabetic status to the general respiratory function we found a negative correlation between baseline FEV1 and glucose levels at 2h after OGTT during PE (r=−0.88, p=0.002).ConclusionIn this pilot study we show that during PE patients with CF and normal glucose tolerance exhibited early latent diabetic glucose intolerance. As this hyperglycemia presents in the later parts of the OGTT it probably results from insufficient second phase insulin secretion during PE. The negative correlation observed here between the diabetic glucose tolerance and FEV1 indicate the need of interventional studies using insulin during PE in non-diabetic patients to determine its potential benefit on the outcome from recurrent PEs

Phospholipase A2 in experimental allergic bronchitis: a lesson from mouse and rat models.

BACKGROUND: Phospholipases A2 (PLA2) hydrolyzes phospholipids, initiating the production of inflammatory lipid mediators. We have previously shown that in rats, sPLA2 and cPLA2 play opposing roles in the pathophysiology of ovalbumin (OVA)-induced experimental allergic bronchitis (OVA-EAB), an asthma model: Upon disease induction sPLA2 expression and production of the broncho-constricting CysLTs are elevated, whereas cPLA2 expression and the broncho-dilating PGE2 production are suppressed. These were reversed upon disease amelioration by treatment with an sPLA2 inhibitor. However, studies in mice reported the involvement of both sPLA2 and cPLA2 in EAB induction. OBJECTIVES: To examine the relevance of mouse and rat models to understanding asthma pathophysiology. METHODS: OVA-EAB was induced in mice using the same methodology applied in rats. Disease and biochemical markers in mice were compared with those in rats. RESULTS: As in rats, EAB in mice was associated with increased mRNA of sPLA2, specifically sPLA2gX, in the lungs, and production of the broncho-constricting eicosanoids CysLTs, PGD2 and TBX2 in bronchoalveolar lavage (BAL). In contrast, EAB in mice was associated also with elevated cPLA2 mRNA and PGE2 production. Yet, treatment with an sPLA2 inhibitor ameliorated the EAB concomitantly with reverting the expression of both cPLA2 and sPLA2, and eicosanoid production. CONCLUSIONS: In both mice and rats sPLA2 is pivotal in OVA-induced EAB. Yet, amelioration of asthma markers in mouse models, and human tissues, was observed also upon cPLA2 inhibition. It is plausible that airway conditions, involving multiple cell types and organs, require the combined action of more than one, essential, PLA2s

Comparison of activity and fatigue of the respiratory muscles and pulmonary characteristics between post-polio patients and controls: A pilot study

<div><p>Objectives</p><p>To compare pulmonary function measures, maximal respiratory pressure and fatigue of respiratory muscles between patients with Post-Polio Syndrome (PPS) and controls.</p><p>Design</p><p>Cross-sectional study.</p><p>Patients</p><p>Patients with PPS (N = 12; age 62.1±11.6 years) able to walk for 6 minutes without human assistance; age-matched controls with no history of polio or pulmonary dysfunction (N = 12; age 62.2±6.5 years).</p><p>Measurements</p><p>A body plethysmograph was used to quantify Residual Volume (RV), Total Lung Capacity (TLC), and Thoracic Gas Volume (TGV) etc. A manometer was used to measure Maximal Inspiratory Pressure (MIP) and Maximal Expiratory Pressure. A spirometer was used to measure Maximal Voluntary Ventilation (MVV). Surface electromyography (sEMG) recorded diaphragmatic muscle activity while performing MVV.</p><p>Results</p><p>The control group had significantly higher TGV and showed improvement in MIP following the effort (difference of 5.5±4.0cmH₂O) while the PPS group showed deterioration in MIP (difference of -2.5±5.0cmH₂O). Subjects with scoliosis had significantly higher RV/TLC values compared with subjects without scoliosis. The 25^th frequency percentile of the sEMG signal acquired during MVV was reduced in the PPS group.</p><p>Conclusions</p><p>Maximal respiratory pressure test and sEMG measurements may identify fatigue of respiratory muscles in patients with PPS. Early diagnosis of respiratory impairment may delay respiratory decline and future need of invasive respiratory aids.</p></div

Triphala (PADMA) extract alleviates bronchial hyperreactivity in a mouse model through liver and spleen immune modulation and increased anti-oxidative effects

Objectives: Triphala (TRP), a herbal extract from Tibetan medicine, has been shown to affect lymphocytes and natural killer T (NKT) cell function. We hypothesize that TRP could ameliorate bronchial hyperreactivity through immune-cell modulations. Methods: Asthma mouse models were generated through intraperitoneal (IP) injections of ovalbumin (OVA)/2 weeks followed by repeated intranasal OVA challenges. Mice were then treated with normal saline (OVA/NS) or Triphala (OVA/TRP). Data were compared with mice treated with inhaled budesonide. All groups were assessed for allergen-induced hyperreactivity; lymphocytes from lungs, livers and spleens were analyzed for OVA-induced proliferation and their alterations were determined by flow cytometry. Oxidative reactivity using chemiluminescence, serum anti-OVA antibodies level and lung histology were assessed. Results: Both TRP and budesonide significantly ameliorated functional and histological OVA-induced bronchial hyperreactivity. TRP had no effect on serum anti-OVA antibodies as compared with decreased levels following budesonide treatment. Furthermore, a significant increase in lung and spleen CD4 counts and a decrease in the liver were noted after TRP treatments. Bronchoalveolar fluid from TRP-treated animals but not from the budesonide-treated animals showed anti-oxidative effects. Conclusion: TRP and budesonide caused a significant decrease in bronchial reactivity. TRP treatment altered immune-cell distributions and showed anti-oxidative properties. These findings suggest that immune-cell modulation with TRP can ameliorate lung injury

Root mean square (RMS) and frequency quartiles (25, 50, and 75) 0f the electromyography (EMG) signal acquired during Maximal Voluntary Ventilation (MVV) in the Post Polio Syndrome (PPS) group and the control group.

<p>Values are presented as mean ± standard deviation.</p

Personal characteristics of the Post Polio Syndrome (PPS) group and the control group.

<p>Numeric values are presented as mean ± standard deviation. Other data are presented as the number of subjects (percent of each group; N = 12).</p