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BMC Pediatrics May 2024Cough variant asthma (CVA) is one of the most common causes of chronic cough in children worldwide. The diagnosis of CVA in children remains challenging. This study...
BACKGROUND
Cough variant asthma (CVA) is one of the most common causes of chronic cough in children worldwide. The diagnosis of CVA in children remains challenging. This study aimed to assess the diagnostic utility of impulse oscillometry (IOS) pulmonary function in children with CVA.
METHODS
This study included children aged 4 to 12 years diagnosed with CVA who underwent IOS pulmonary function and bronchodilation (BD) tests. A control group of healthy children was matched. Pre- and post-BD IOS parameters were recorded and presented as mean ± standard deviation or median. Receiver operating characteristic (ROC) curves were plotted, and the area under the curve (AUC) was calculated to evaluate the discriminatory potential of the IOS parameters for diagnosing CVA.
RESULTS
A total of 180 patients with CVA and 65 control subjects were included. The baseline IOS parameters in the CVA group, except X5%pred, were significantly greater compared to the control group. After inhalation of salbutamol sulfate, all IOS parameters improved significantly in the CVA group. However, Z5%pred, R5%pred, and R20%pred remained greater in the CVA group compared to the control group. The improvement rates of IOS parameters in the CVA group significantly surpassed those in the control group. The ROC curve results for pre-BD IOS parameters and the improvement rate during the BD test showed that the combinations of pre-Z5%pred+Z5% and pre-R5%pred+R5% achieved the highest AUC value of 0.920 and 0.898, respectively. The AUC values of these combined parameters surpassed those of individual ones.
CONCLUSIONS
This study highlights that children with CVA exhibit greater IOS parameters compared to healthy children. The changes in IOS parameters during the BD test provided valuable diagnostic information for CVA, and the combination of various parameters can help pediatricians accurately identify CVA in children.
Topics: Humans; Cough; Child; Asthma; Male; Female; Oscillometry; Child, Preschool; Case-Control Studies; ROC Curve; Albuterol; Respiratory Function Tests; Bronchodilator Agents; Cough-Variant Asthma
PubMed: 38702638
DOI: 10.1186/s12887-024-04749-4 -
Therapeutic Advances in Respiratory... 2024This summary describes the results of a clinical study called MANDALA that was published in the in 2022. In the MANDALA study, researchers looked at a new asthma rescue... (Review)
Review
This summary describes the results of a clinical study called MANDALA that was published in the in 2022. In the MANDALA study, researchers looked at a new asthma rescue inhaler that contains both and in a single inhaler (known as , AIRSUPRA™). This summary describes the results for people aged 18 yearsand older who took part in the study.
Topics: Humans; Asthma; Albuterol; Drug Combinations; Administration, Inhalation; Bronchodilator Agents; Budesonide; Adult; Middle Aged; Male; Female; Nebulizers and Vaporizers; Treatment Outcome; Adolescent; Young Adult; Aged; Anti-Asthmatic Agents
PubMed: 38698565
DOI: 10.1177/17534666241232264 -
Jornal de Pediatria Apr 2024To compare the effectiveness of inhaled Magnesium Sulfate associated with Salbutamol versus Inhaled Salbutamol alone in patients with moderate and severe asthma...
OBJECTIVE
To compare the effectiveness of inhaled Magnesium Sulfate associated with Salbutamol versus Inhaled Salbutamol alone in patients with moderate and severe asthma exacerbations.
METHOD
Clinical, prospective and randomized study with patients between 3 and 14 years of age divided into two groups: one to receive inhaled salbutamol associated with magnesium sulfate (GSM), the other to receive inhaled salbutamol alone (GS). The sample consisted of 40 patients, 20 patients in each group. Severity was classified using the modified Wood-Downes score, with values between 4 and 7 classified as moderate and 8 or more classified as severe.
RESULTS
Post-inhalation scores decreased both in patients who received salbutamol and magnesium and in those who received salbutamol alone, with no statistically significant difference between the groups.
CONCLUSIONS
Despite the benefits when administered intravenously, inhalation of the drug alone or in combination did not reduce the severity of the exacerbation.
PubMed: 38693043
DOI: 10.1016/j.jped.2024.03.012 -
Journal of Aerosol Medicine and... May 2024To evaluate the safety and efficacy of 2.5 and 1.25 mg nebulized salbutamol on Transient Tachypnea of the Newborn (TTN) compared with placebo. We conducted a...
Safety and Efficacy of 2.5 mg and 1.25 mg Nebulized Salbutamol Compared with Placebo on Transient Tachypnea of the Newborns: A Triple-Blind Phase II/III Parallel Randomized Controlled Trial.
To evaluate the safety and efficacy of 2.5 and 1.25 mg nebulized salbutamol on Transient Tachypnea of the Newborn (TTN) compared with placebo. We conducted a triple-blind, phase II/III parallel randomized controlled trial in two university-affiliated hospitals with neonatal intensive care units. Newborns with a confirmed diagnosis of TTN, with gestational age >35 weeks and gestational weight >2 kg were included. Cases of asphyxia, meconium aspiration syndrome, and persistent pulmonary hypertension were excluded. Ninety eligible patients were randomly allocated in three intervention groups (2.5 mg salbutamol, 1.25 mg salbutamol, and placebo), and a single-dose nebulized product was prescribed 6 hours after the birth. Safety outcomes included postintervention tachycardia, hyperglycemia, hypokalemia, and changes in blood pressure. To evaluate the efficacy, the duration of postintervention tachypnea, TTN clinical score, and clinical and paraclinical respiratory indices were assessed. Parents, Outcome assessors, and data analyzer were blind to the intervention. There was no adverse reaction, including tachycardia, hypokalemia, and jitteriness. Both groups of salbutamol recipients showed significant improvement regarding respiratory rate, TTN clinical score, and oxygenation indices compared with the placebo (-values <0.001). Nonstatistically significant higher hospital stay was observed in the placebo group. Single 2.5 mg salbutamol nebulization showed a little better outcome than the dose of 1.25 mg, although we could not find statistical superiority. The newly applied single high dose of 2.5 mg nebulized salbutamol is safe in treating TTN and leads to notable faster improvement of respiratory status without any considerable adverse reaction. IRCT20190328043133N1.
PubMed: 38687321
DOI: 10.1089/jamp.2023.0043 -
Scientific Reports Apr 2024Fixed dose combinations (FDCs) incorporating two or three medicines in a single inhaler have been created to enhance patient compliance and hence clinical outcomes....
Fixed dose combinations (FDCs) incorporating two or three medicines in a single inhaler have been created to enhance patient compliance and hence clinical outcomes. However, the development of dry powder inhalers (DPIs), particularly for FDCs, faces challenges pertinent to formulation uniformity and reproducibility. Therefore, this project aimed to employ nanotechnology to develop a FDC of DPIs for market-leading medicines-fluticasone propionate (FP) and salmeterol xinafoate (SAL)-for asthma management. Nanoaggregates were prepared using a novel biocompatible and biodegradable poly(ester amide) based on the amino acid tyrosine, utilising a one-step interfacial polymerisation process. The produced tyrosine poly (ester amide) drug-loaded nanoparticles were evaluated for content uniformity, PSA, FTIR, TEM, DSC, XRD and aerodynamic performance (in vitro and in vivo). The optimised formulation demonstrated high entrapment efficiency- > 90%. The aerodynamic performance in terms of the emitted dose, fine particle fraction and respirable dose was superior to the carrier-based marketed product. In-vivo studies showed that FP (above the marketed formulation) and SAL reached the lungs of mice in a reproducible manner. These results highlight the superiority of novel FDC FP/SAL nanoparticles prepared via a one-step process, which can be used as a cost-effective and efficient method to alleviate the burden of asthma.
Topics: Animals; Nanoparticles; Tyrosine; Administration, Inhalation; Lung; Mice; Asthma; Polyesters; Dry Powder Inhalers; Fluticasone; Drug Delivery Systems; Salmeterol Xinafoate; Particle Size; Drug Carriers
PubMed: 38684750
DOI: 10.1038/s41598-024-59588-1 -
NPJ Primary Care Respiratory Medicine Apr 2024Short-acting beta-agonist (SABA) over-use in asthma is harmful for patients and the environment. The Investment and Impact Fund (IIF) 2022/2023 financially rewarded...
Reducing short-acting beta-agonist use in asthma: Impact of national incentives on prescribing practices in England and the findings from SENTINEL Plus early adopter sites.
Short-acting beta-agonist (SABA) over-use in asthma is harmful for patients and the environment. The Investment and Impact Fund (IIF) 2022/2023 financially rewarded English primary care networks that achieved specific targets, including reducing SABA over-use (RESP-02) and lowering the mean carbon footprint per salbutamol inhaler prescribed (ES-02). SENTINEL Plus is a co-designed quality improvement package that aims to improve asthma outcomes and reduce asthma's environmental impact by addressing SABA over-use. We investigated the impact of (i) the IIF incentives and (ii) SENTINEL Plus implementation on asthma prescribing. Using Openprescribing.net data, we demonstrate that IIF 2022-2023 had no significant impact on the total number of SABA prescribed in England (25,927,252 during 12-months pre- and 25,885,213 12-months post-IIF; 0.16% decrease; p=NS), but lower carbon footprint SABA inhaler use increased (Salamol™ prescribing increased from 5.1% to 19% of SABA prescriptions, p < 0.01). In contrast, SENTINEL Plus sites significantly reduced SABA prescribing post-implementation (5.43% decrease, p < 0.05).
Topics: Humans; Adrenergic beta-Agonists; Albuterol; Anti-Asthmatic Agents; Asthma; England; Practice Patterns, Physicians'; Primary Health Care; Quality Improvement
PubMed: 38684652
DOI: 10.1038/s41533-024-00363-0 -
The AAPS Journal Apr 2024Advair Diskus is an essential treatment for asthma and chronic obstructive pulmonary disease. It is a dry powder inhaler with a combination of fluticasone propionate... (Randomized Controlled Trial)
Randomized Controlled Trial
Advair Diskus is an essential treatment for asthma and chronic obstructive pulmonary disease. It is a dry powder inhaler with a combination of fluticasone propionate (FP) and salmeterol xinafoate (SX). However, the pharmacokinetics (PK) batch-to-batch variability of the reference-listed drug (RLD) hindered its generic product development. This work developed the PK models for inhaled FP and SX that could represent potential batch variability. Two batches each of the reference and the test product (R, R, T, T) of Advair Diskus (100 μg FP/50 μg SX inhalation) were administered to 60 healthy subjects in a 4-period, 4-sequence crossover study. The failure of the bioequivalence (BE) between R and R confirmed the high between-batch variability of the RLD. Non-linear mixed effect modeling was used to estimate the population mean PK parameters for each batch. For FP, a 2-compartment model with a sequential dual zero-order absorption best described the PK profile. For SX, a 2-compartment model with a first-order absorption model best fit the data. Both models were able to capture the plasma concentration, the maximum concentration, and the total exposure (AUC) adequately for each batch, which could be used to simulate the BE study in the future. In vitro properties were also measured for each batch, and the batch with a higher fraction of the fine particle (diameter < 1 µm, < 2 µm) had a higher AUC. This positive correlation for both FP and SX could potentially assist the batch selection for the PK BE study.
Topics: Humans; Administration, Inhalation; Cross-Over Studies; Male; Adult; Fluticasone-Salmeterol Drug Combination; Models, Biological; Therapeutic Equivalency; Young Adult; Dry Powder Inhalers; Bronchodilator Agents; Female; Middle Aged; Fluticasone; Salmeterol Xinafoate; Healthy Volunteers
PubMed: 38671158
DOI: 10.1208/s12248-024-00913-x -
Neuromuscular Disorders : NMD Jun 2024Recessive desminopathies are rare and often present as severe early-onset myopathy. Here we report a milder phenotype in three unrelated patients from southern India (2...
Recessive desminopathies are rare and often present as severe early-onset myopathy. Here we report a milder phenotype in three unrelated patients from southern India (2 M, 1F) aged 16, 21, and 22 years, who presented with childhood-onset, gradually progressive, fatigable limb-girdle weakness, ptosis, speech and swallowing difficulties, without cardiac involvement. Serum creatine kinase was elevated, and repetitive nerve stimulation showed decrement in all. Clinical improvement was noted with pyridostigmine and salbutamol in two patients. All three patients had a homozygous substitution in intron 5: DES(NM_001927.4):c.1023+5G>A, predicted to cause a donor splice site defect. Muscle biopsy with ultrastructural analysis suggested myopathy with myofibrillar disarray, and immunohistochemistry showed partial loss of desmin with some residual staining, while western blot analysis showed reduced desmin. RT-PCR of patient muscle RNA revealed two transcripts: a reduced normal desmin transcript and a larger abnormal transcript suggesting leaky splicing at the intron 5 donor site. Sequencing of the PCR products confirmed the inclusion of intron 5 in the longer transcript, predicted to cause a premature stop codon. Thus, we provide evidence for a leaky splice site causing partial loss of desmin associated with a unique phenotypic presentation of a milder form of desmin-related recessive myopathy overlapping with congenital myasthenic syndrome.
Topics: Humans; Male; Desmin; Female; Young Adult; Adolescent; Muscle, Skeletal; RNA Splice Sites; Synaptic Transmission; Phenotype; Mutation
PubMed: 38669730
DOI: 10.1016/j.nmd.2024.03.011 -
Cureus Mar 2024Neonatal hypotonia presents with low muscle tone and an array of symptoms that vary depending on the etiology. The differential diagnosis for this condition is complex....
Neonatal hypotonia presents with low muscle tone and an array of symptoms that vary depending on the etiology. The differential diagnosis for this condition is complex. It is crucial to exclude life-threatening causes before following a diagnostic algorithm and performing additional tests. Given the wide range of clinical symptoms and etiologies for neonatal hypotonia, rapid genetic testing has the potential to expedite diagnosis, reduce invasive testing such as muscle biopsy, reduce hospital stays, and guide condition management. A four-week-old girl was admitted to the emergency department (ED) with a one-day history of lethargy, poor feeding, congestion, cough, and hypoxemia. Given positive rhino-enterovirus testing and high inflammatory markers, antibiotics were administered. Imaging, venous blood gas, and blood cultures were negative, and the patient was admitted to the pediatric intensive care unit (PICU) for hypoxemia. After speech-language pathology (SLP) and occupational therapy (OT) evaluation, weak orofacial muscles and feeding issues resulted in a nasogastric tube placement. A swallow study revealed decreased pharyngeal contraction and post-swallow liquid residue. Laryngoscopy showed mild laryngomalacia and dysphagia with aspiration. Genetic testing identified an ACTA1 mutation and confirmed nemaline myopathy (NM). The patient's oxygen levels dropped further during sleep, resulting in diagnoses of severe obstructive and moderate-severe central sleep apnea. Treatment included oxygen therapy, SLP, physical therapy, albuterol, and cough assists. After discharge, the patient was frequently re-admitted with chronic respiratory failure and bronchiolitis and later had gastrostomy and tracheostomy tubes inserted. This specific case highlights the importance of implementing a diagnostic algorithm for neonatal hypotonia. It is also important for physicians, especially emergency medicine (EM) providers, to first exclude infection, sepsis, and cardiac and respiratory organ failure before looking into other tests. Then, physicians should evaluate for more rare etiologies. In this patient's case, the hypotonia was due to a rare genetic disease, nemaline myopathy, and a multidisciplinary approach was used for this patient's care.
PubMed: 38659511
DOI: 10.7759/cureus.56866 -
Revista Espanola de Anestesiologia Y... Apr 2024Patients with status asthmaticus (SA) frequently present with lactic acidosis (LA). Our goal is to identify the nature of this LA using the Stewart physicochemical model...
BACKGROUND
Patients with status asthmaticus (SA) frequently present with lactic acidosis (LA). Our goal is to identify the nature of this LA using the Stewart physicochemical model and to identify the independent factors associated with LA in children with SA.
METHODS
Analytical study of a retrospective cohort using a nested case-control design. Twenty-eight episodes of SA in 24 children were included. Patients admitted to a paediatric intensive care unit (PICU) for SA over a 9-year period were recruited consecutively. Data were analysed using the Stewart model and the Strong Ion Calculator. Data were analysed using descriptive statistics and regression models were fitted within the general linear model.
RESULTS
Hyperlacticaemia (Lact[mM/L] = 3.905 [95% CI = 3.018-4.792]) and acidosis (pH = 7.294 [95% CI = 7.241-7.339]) were observed in 18 episodes (15 patients; 62.5%). According to the Stewart model, acidosis was caused by a decrease in strong ion difference. Initially, pCO2 was high (pCO2[mmHg] = 45.806 [95% CI = 37.314-54.298]) but the net unmeasured ion (NUI) component was normal (NUI = -4,461 [95% CI = -3.51 to -5.412]), and neither changed significantly over the clinical course. There was no need to determine pyruvate, as the NUI was normal and the LA was type B (non-hypoxic, lactate/pyruvate < 25). We observed a correlation (P = .023) between LA and intramuscular epinephrine administered on arrival at hospital, but not between LA and the cumulative dose of nebulized salbutamol.
CONCLUSIONS
Most patients with SA presented LA. The Stewart model confirmed that LA is not hypoxic, probably due to sympathomimetic-related glycolysis.
PubMed: 38657950
DOI: 10.1016/j.redare.2024.04.010