Asthma and COVID-19: In Defense of Evidence-Based SABA.

There have recently been major objections to the use of short-acting beta-agonist (SABA) in episodic acute asthma culminating in a call for replacing SABA with combination of inhaled corticosteroids and long-acting beta-agonists despite little evidence supporting this point of view. It is regrettable to note that this attack on SABA occurs in the midst of an unprecedented demand for, and shortage of, SABA inhalers during the current COVID-19 pandemic, and the worldwide efforts to increase SABA supplies. In this commentary, we defend the well-established role of SABA and argue that the call for the phase out of SABA is inappropriate, since it is not solidly evidence based.

Evaluation of clinically and physiologically atypical asthma: If it doesn't wheeze it may still be asthma.

OBJECTIVE: Children with asthma-like symptoms may not clinically wheeze. The objectives of this study were to evaluate if children, without physician-documented wheeze, wheeze during bronchial-challenge-testing (BCT), and if measurements of O2Sat and respiratory rate during BCT improve the BCT sensitivity? METHODS: Seven hundred and twenty-four children, who were referred for suspicion of asthma, performed a BCT. Positive BCT was determined by the provocation concentration (PC) which resulted in a 20% decrease in FEV1 (PC20), (in those who were able to perform spirometry, group B), or (in those unable to perform spirometry, group A) a 50% increase in respiratory rate (PCRR), or a 5% decrease in oxygen-saturation (PCO2-Sat) or appearance of wheezing (PCwheeze). RESULTS: Five hundred and seven BCTs were positive: group A n = 89 age, median (IQR), 3 (2.5-3.7) years (17.6%), were unable to perform spirometry, and group B n = 418 age 10.7 (6.8-15.6) years (82.4%), were able to perform spirometry. Children, without physician-documented wheeze in the total population (groups A plus B), were more likely (65.5%) to have a positive BCT without wheeze compared with those with physician-documented wheeze (41.0%, P < 0.001). In group A, adding PCRR and PCO2-Sat increased BCT sensitivity by 23.6%. CONCLUSIONS: Many children in both groups did not wheeze despite reaching BCT endpoints. Children without physician-documented wheeze tended not to wheeze at BCT. This may result in clinical under-diagnosis of asthma if depending on the presence of wheeze. In young children, adding PCRR and PCO2-Sat substantially increases BCT sensitivity and may improve asthma diagnosis.

More Realistic Face Model Surface Improves Relevance of Pediatric In-Vitro Aerosol Studies.

BACKGROUND: Various hard face models are commonly used to evaluate the efficiency of aerosol face masks. Softer more realistic "face" surface materials, like skin, deform upon mask application and should provide more relevant in-vitro tests. Studies that simultaneously take into consideration many of the factors characteristic of the in vivo face are lacking. These include airways, various application forces, comparison of various devices, comparison with a hard-surface model and use of a more representative model face based on large numbers of actual faces. AIM: To compare mask to "face" seal and aerosol delivery of two pediatric masks using a soft vs. a hard, appropriately representative, pediatric face model under various applied forces. METHODS: Two identical face models and upper airways replicas were constructed, the only difference being the suppleness and compressibility of the surface layer of the "face." Integrity of the seal and aerosol delivery of two different masks [AeroChamber (AC) and SootherMask (SM)] were compared using a breath simulator, filter collection and realistic applied forces. RESULTS: The soft "face" significantly increased the delivery efficiency and the sealing characteristics of both masks. Aerosol delivery with the soft "face" was significantly greater for the SM compared to the AC (p< 0.01). No statistically significant difference between the two masks was observed with the hard "face." CONCLUSIONS: The material and pliability of the model "face" surface has a significant influence on both the seal and delivery efficiency of face masks. This finding should be taken into account during in-vitro aerosol studies.

Computerized Dead-Space Volume Measurement of Face Masks Applied to Simulated Faces.

BACKGROUND: The dead-space volume (VD) of face masks for metered-dose inhaler treatments is particularly important in infants and young children with asthma, who have relatively low tidal volumes. Data about VD have been traditionally obtained from water displacement measurements, in which masks are held against a flat surface. Because, in real life, masks are placed against the face, VD is likely to differ considerably between masks depending upon their contour and fit. The aim of this study was to develop an accurate and reliable way to measure VD electronically and to apply this technique by comparing the electronic VD of commonly available face masks. METHODS: Average digital faces were obtained from 3-dimensional images of 270 infants and children. Commonly used face masks (small and medium) from various manufacturers (Monaghan Medical, Pari Respiratory Equipment, Philips Respironics, and InspiRx) were scanned and digitized by means of computed tomography. Each mask was electronically applied to its respective digital face, and the VD enclosed (mL) was computerized and precisely measured. RESULTS: VD varied between 22.6 mL (SootherMask, InspiRx) and 43.1 mL (Vortex, Pari) for small masks and between 41.7 mL (SootherMask) and 71.5 mL (AeroChamber, Monaghan Medical) for medium masks. These values were significantly lower and less variable than measurements obtained by water displacement. CONCLUSIONS: Computerized techniques provide an innovative and relatively simple way of accurately measuring the VD of face masks applied to digital faces. As determined by computerized measurement using average-size virtual faces, the InspiRx masks had a significantly smaller VD for both small and medium masks compared with the other masks. This is of considerable importance with respect to aerosol dose and delivery time, particularly in young children. (ClinicalTrials.gov registration NCT01274299.).

Nasal versus oral aerosol delivery to the "lungs" in infants and toddlers.

OBJECTIVES: The oral route has been considered superior to the nasal route for aerosol delivery to the lower respiratory tract (LRT) in adults and children. However, there are no data comparing aerosol delivery via the oral and nasal routes in infants. The aim of this study was to compare nasal and oral delivery of aerosol in anatomically correct replicas of infants' faces containing both nasal and oral upper airways. METHODS: Three CT-derived upper respiratory tract ("URT") replicas representing infants/toddlers aged 5, 14 and 20 months were studied and aerosol delivery to the "lower respiratory tract" (LRT) by either the oral or nasal route for each of the replicas was measured at the "tracheal" opening. A radio-labeled (99mDTPA) normal saline solution aerosol was generated by a soft-mist inhaler (SMIRespimat® Boehringer Ingelheim, Germany) and aerosol was delivered via a valved holding chamber (Respichamber® TMI, London, Canada) and an air-tight mask (Unomedical, Inc., McAllen, TX). A breath simulator was connected to the replicas and an absolute filter at the "tracheal" opening captured the aerosol representing "LRT" dose. Age-appropriate mask dimensions and breathing patterns were employed for each of the airway replicas. Two different tidal volumes (Vt ) were used for comparing the nasal versus oral routes. RESULTS: Nasal delivery to the LRT exceeded that of oral delivery in the 5- and 14-month models and was equivalent in the 20-month model. Differences between nasal and oral delivery diminished with "age"/size. Similar findings were observed with lower and higher tidal volumes (Vt ). CONCLUSION: Nasal breathing for aerosol delivery to the "LRT" is similar to, or more efficient than, mouth breathing in infant/toddler models, contrary to what is observed in older children and adults. Pediatr Pulmonol. 2015; 50:276-283. © 2014 Wiley Periodicals, Inc.

Feasibility of aerosol drug delivery to sleeping infants: a prospective observational study.

OBJECTIVES: Delivery of inhaled medications to infants is usually very demanding and is often associated with crying and mask rejection. It has been suggested that aerosol administration during sleep may be an attractive alternative. Previous studies in sleeping children were disappointing as most of the children awoke and rejected the treatment. The SootherMask (SM) is a new, gentle and innovative approach for delivering inhaled medication to infants and toddlers. The present pilot study describes the feasibility of administering inhaled medications during sleep using the SM. DESIGN: Prospective observational study. SETTING: Out patients. PARTICIPANTS: 13 sleeping infants with recurrent wheezing who regularly used pacifiers and were <12 months old. INTERVENTION: Participants inhaled technetium99mDTPA-labelled normal saline aerosol delivered via a Respimat Soft Mist Inhaler (SMI) (Boehringer-Ingelheim, Germany) and SM + InspiraChamber (IC; InspiRx Inc, New Jersey, USA). OUTCOMES: The two major outcomes were the acceptability of the treatment and the lung deposition (per cent of emitted dose). RESULTS: All infants who fulfilled the inclusion criteria successfully received the SM treatment during sleep without difficulty. Mean lung deposition (±SD) averaged 1.6±0.5% in the right lung. CONCLUSIONS: This study demonstrated that the combination of Respimat, IC and SM was able to administer aerosol therapy to all the sleeping infants who were regular pacifier users with good lung deposition. Administration of aerosols during sleep is advantageous since all the sleeping children accepted the mask and ensuing aerosol therapy under these conditions, in contrast to previous studies in which there was frequent mask rejection using currently available devices. CLINICAL TRIAL REGISTRY: NCT01120938.

Design of aerosol face masks for children using computerized 3D face analysis.

BACKGROUND: Aerosol masks were originally developed for adults and downsized for children. Overall fit to minimize dead space and a tight seal are problematic, because children's faces undergo rapid and marked topographic and internal anthropometric changes in their first few months/years of life. Facial three-dimensional (3D) anthropometric data were used to design an optimized pediatric mask. METHODS: Children's faces (n=271, aged 1 month to 4 years) were scanned with 3D technology. Data for the distance from the bridge of the nose to the tip of the chin (H) and the width of the mouth opening (W) were used to categorize the scans into "small," "medium," and "large" "clusters." RESULTS: "Average" masks were developed from each cluster to provide an optimal seal with minimal dead space. The resulting computerized contour, W and H, were used to develop the SootherMask® that enables children, "suckling" on their own pacifier, to keep the mask on their face, mainly by means of subatmospheric pressure. The relatively wide and flexible rim of the mask accommodates variations in facial size within and between clusters. CONCLUSIONS: Unique pediatric face masks were developed based on anthropometric data obtained through computerized 3D face analysis. These masks follow facial contours and gently seal to the child's face, and thus may minimize aerosol leakage and dead space.

Deposition of small particles in the developing lung.

Infancy is a time of marked and rapid changes in respiratory tract development. Infants (0-1 year of age) and young children (1- 3 years of age) are a unique subpopulation with regard to therapeutic aerosols. Anatomical, physiological and emotional factors, peculiar to these age groups, present significant challenges for aerosol delivery to the respiratory tract. Most studies with inhaled corticosteroids (ICS) have administered aerosols with relatively large particles, frequently > 3 µm in mass median aerodynamic diameter (MMAD). These drugs were designed for use in adults and older children and were administered with masks which were frequently rejected by children under age 3-4 years. We review the reasons that large-particle aerosols are likely to be less effective in infants and young children. We suggest that the benefit of inhaled medications in this age group requires further evaluation to determine if better therapeutic outcomes might be achieved using smaller particles and more patient-friendly delivery systems.

Lung aerosol deposition in suckling infants.

INTRODUCTION: Aerosol therapy in infants may be greatly compromised by face mask rejection due to squirming and crying. Lung aerosol deposition in crying infants may thereby be greatly reduced. Since 'suckling' on a pacifier calms infants, they should more readily accept a face mask that incorporates a pacifier. However, since infants must breathe nasally while suckling, lung aerosol deposition may be reduced due to impaction in the nose. The aim of the present pilot study was to compare lung aerosol deposition while suckling on a pacifier incorporated into a mask with that obtained while inhaling from a conventional mask. METHODS: Twelve infants <12 months old and who regularly used pacifiers participated as their own controls. Lung aerosol deposition was measured scintigraphically (technetium-(99m)DTPA-labelled normal saline aerosol, MMAD (Mass Median Aerodynamic Diameter) 3 um and GSD (Geometric Standard Deviation) of 2) via jet nebuliser using a conventional mask versus 'suckling' on their pacifier incorporated into a unique mask. RESULTS: Mean lung deposition (± SD) while suckling using a mask with attached pacifier (1.6 ± 0.5% in the right lung) was similar to that with a conventional mask (1.7 ± 0.9%, p=0.81). CONCLUSIONS: Lung aerosol deposition during nasal breathing while suckling on a pacifier-equipped mask is similar to that in infants breathing quietly using a conventional mask, and results comparable with previous data in infants and in nasal breathing models of an infant's upper respiratory tract. Using a pacifier during aerosol treatment in infants may be as efficient as conventional treatment without a pacifier.