Obligate Nose Breathers Research Articles

Nasal accumulation and metabolism of Δ9-tetrahydrocannabinol following aerosol (‘vaping’) administration in an adolescent rat model

Passive aerosol exposure to Δ9-tetrahydrocannabinol (THC) in laboratory animals results in faster onset of action and less extensive liver metabolism compared to most other administration routes and might thus provide an ecologically relevant model of human cannabis inhalation. Previous studies have, however, overlooked the possibility that rodents, as obligate nose breathers, may accumulate aerosolized THC in the nasal cavity, from where the drug might directly diffuse to the brain. To test this, we administered THC (ten 5-s puffs of 100 mg/mL of THC) to adolescent (31-day-old) Sprague-Dawley rats of both sexes. We used liquid chromatography/tandem mass spectrometry to quantify the drug and its first-pass metabolites – 11-hydroxy-Δ9-THC (11-OH-THC) and 11-nor-9-carboxy-Δ9-THC (11-COOH-THC) – in nasal mucosa, lungs, plasma, and brain (olfactory bulb and cerebellum) at various time points after exposure. Apparent maximal THC concentration and area under the curve were ∼5 times higher in nasal mucosa than in lungs and 50–80 times higher than in plasma. Concentrations of 11-OH-THC were also greater in nasal mucosa and lungs than other tissues, whereas 11-COOH-THC was consistently undetectable. Experiments with microsomal preparations confirmed local metabolism of THC into 11-OH-THC (not 11-COOH-THC) in nasal mucosa and lungs. Finally, whole-body exposure to THC deposited substantial amounts of THC (∼150 mg/g) on fur but suppressed post-exposure grooming in rats of both sexes. The results indicate that THC absorption and metabolism in nasal mucosa and lungs, but probably not gastrointestinal tract, contribute to the pharmacological effects of aerosolized THC in male and female rats.

Ventilation via nose cone results in similar hemodynamic parameters and blood gas levels as endotracheal intubation during open chest surgery in rats.

Open chest surgery in rodents requires assisted breathing and the most common approach for ventilation is via an endotracheal tube. Even with well-trained operators the endotracheal intubation is technically challenging and may lead to prolonged procedures and endotracheal intubation complications. Nose cone ventilation is a simpler procedure compared to endotracheal intubation and has the potential to improve animal welfare by reducing procedure time and endotracheal intubation associated complications. Rats are obligate nose breathers, and therefore replacing intubation with air supply from a nose cone would be an advantage and a more natural way of breathing. Here, we compared the values for several blood gases, blood pressure and heart rate from rats that were nose cone ventilated with rats that underwent endotracheal intubation at 12 timepoints equally distributed across three surgical stages: baseline, open chest and closed chest. Throughout the monitoring period the hemodynamic and blood gas values for both methods of ventilation were within published, normal ranges for the rat and were biologically equivalent (equivalence test p value ≤ 0.05). Our data showed that nose cone ventilation-maintained blood gases and hemodynamic homeostasis equivalent to endotracheal intubation. Nose cone ventilation can be recommended as an alternative to endotracheal intubation in rat experiments where investigators require airway control.

Bilateral Complete Congenital Choanal Atresia in an 18-month-old Female Child with Rare Clinical Presentation: Transnasal Endoscopic Repair with Stent

ABSTRACT Congenital choanal atresia (CCA) is the developmental failure of the nasal cavity to communicate with the nasopharynx. Surgical repair is recommended in the first weeks of life in bilateral congenital choanal atresia (BCCA), because this is a life-threatening situation in newborns as they are obligate nose breathers. This article reports on an 18-month-old female child, with delayed presentation of bilateral choanal atresia, treated successfully endoscopically and stent placement postoperatively. Case report The patient is an 18-month-old female child, born full term, by cesarean section (for cephalopelvic disproportion) with birth weight 3,750 gm to a 30-year-old primigravida. There were no immediate prenatal or postnatal medical or surgical problems in the mother. The child cried immediately after birth, there was no postnatal respiratory distress, cyanosis, or any major hospital admission. On examination, microcephaly (head circumference 46 cm below 2 standard deviation of the mean), hypertelorism, ani-Mongolian slanted eyes, left side cleft lip with high arched palate with malocclusion were observed. She presented late with c/o nasal discharge and mild breathing difficulty on breastfeeding. The catheter test revealed the diagnosis of BCCA. Noncontrast computed tomography (CT) scan nose was done, which showed nonposterior choana blocked with bony plates on both the sides (Fig. 1). The paranasal sinuses, orbit, and anterior nasal cavities were within normal limits. Transnasal endoscopic repair was done under general anesthesia. Endoscopy revealed a bony atresia (Fig. 2), which was drilled out keeping the direction medially and inferiorly. Feeding tubes were fashioned as stents and placed for a period of 6 weeks. There were no postoperative complications. The patient was referred to pediatric surgery for other problems. Endoscopy confirmed bilateral patency at 12 weeks postoperatively. How to cite this article Mohindra S, Gupta AK. Bilateral Complete Congenital Choanal Atresia in an 18-month-old Female Child with Rare Clinical Presentation: Transnasal Endoscopic Repair with Stent. Clin Rhinol An Int J 2016;9(3):153-154.

Mammalian Cell-Derived Respiratory Syncytial Virus-Like Particles Protect the Lower as well as the Upper Respiratory Tract.

Globally, Respiratory Syncytial Virus (RSV) is a leading cause of bronchiolitis and pneumonia in children less than one year of age and in USA alone, between 85,000 and 144,000 infants are hospitalized every year. To date, there is no licensed vaccine. We have evaluated vaccine potential of mammalian cell-derived native RSV virus-like particles (RSV VLPs) composed of the two surface glycoproteins G and F, and the matrix protein M. Results of in vitro testing showed that the VLPs were functionally assembled and immunoreactive, and that the recombinantly expressed F protein was cleaved intracellularly similarly to the virus-synthesized F protein to produce the F1 and F2 subunits; the presence of the F1 fragment is critical for vaccine development since all the neutralizing epitopes present in the F protein are embedded in this fragment. Additional in vitro testing in human macrophage cell line THP-1 showed that both virus and the VLPs were sensed by TLR-4 and induced a Th1-biased cytokine response. Cotton rats vaccinated with RSV VLPs adjuvanted with alum and monophosphoryl lipid A induced potent neutralizing antibody response, and conferred protection in the lower as well as the upper respiratory tract based on substantial virus clearance from these sites. To the best of our knowledge, this is the first VLP/virosome vaccine study reporting protection of the lower as well as the upper respiratory tract: Prevention from replication in the nose is an important consideration if the target population is infants < 6 months of age. This is because continued virus replication in the nose results in nasal congestion and babies at this age are obligate nose breathers. In conclusion, these results taken together suggest that our VLPs show promise to be a safe and effective vaccine for RSV.

In Vitro Evaluation of Aerosols Delivered via the Nasal Route.

Infants and young children are obligate nose breathers; therefore, a transnasal route seems the logical delivery method of inhaled aerosols. The efficiency of aerosol delivery depends on several factors, such as interface, type of nebulizer, and patient age and breathing pattern. We hypothesized that the use of a vibrating mesh nebulizer, a tight-fitting face mask, and a head model and breathing pattern of an older child would result in a higher lung dose. We also hypothesized that the use of an anatomically correct model would more accurately reflect lung dose than models that do not include airways. A model comprising a breathing simulator and an anatomically correct model of a 7-month-old infant and a 5-y-old child with an interposed collection filter (lung dose) were used. Breathing patterns of a newborn, infant, and child were used with 7 interfaces. A continuous output and a vibrating mesh nebulizer were loaded with albuterol sulfate solution (5 mg/3.5 mL) and operated for 5 min. Albuterol mass was determined via spectrophotometer (276 nm). Lung dose varied between 0 and 3%. The jet nebulizer was more efficient than the vibrating mesh nebulizer. The front-loaded mask was the most efficient interface. We also found that higher tidal volumes were associated with higher lung doses and that the use of a larger airway model resulted in a lower lung dose. Finally, the model showed a good correlation with in vivo data and rendered lung doses severalfold lower than previous data obtained with oral models. Careful pairing of the aerosol generator and interface is very important during transnasal aerosol delivery.

It Takes a Mouth to Eat and a Nose to Breathe: Abnormal Oral Respiration Affects Neonates' Oral Competence and Systemic Adaptation

Mammalian, including human, neonates are considered to be obligate nose breathers. When constrained to breathe through their mouth in response to obstructed or closed nasal passages, the effects are pervasive and profound, and sometimes last into adulthood. The present paper briefly surveys neonates' and infants' responses to this atypical mobilisation of the mouth for breathing and focuses on comparisons between human newborns and infants and the neonatal rat model. We present the effects of forced oral breathing on neonatal rats induced by experimental nasal obstruction. We assessed the multilevel consequences on physiological, structural, and behavioural variables, both during and after the obstruction episode. The effects of the compensatory mobilisation of oral resources for breathing are discussed in the light of the adaptive development of oromotor functions.

404: Effects of Intranasal Oxymetazoline on the Pediatric Population Aged 1 to 12 Month: An Interim Analysis

Young children are obligate nose breathers. When these patients develop severe congestion, they can present to the emergency department (ED) with difficulty feeding, tachypnea, retractions, and respiratory distress, despite nasal saline and suction at home. Intranasal oxymetazoline has been used in the adult population to counter congestion with a minimal side effect profile. It can offer an alternative management for parents and physicians. This is a preliminary safety study of using oxymetazoline in the pediatric population with the hypothesis that medication administration will not have a significant side effect on heart rate, blood pressure, or respiratory rate, and can be a safe treatment option for children 1 month to 12 months old.

Assessment of Upper Respiratory Tract and Ocular Irritative Effects of Volatile Chemicals in Humans

ABSTRACTAccurate assessment of upper respiratory tract and ocular irritation is critical for identifying and remedying problems related to overexposure to volatile chemicals, as well as for establishing parameters of irritation useful for regulatory purposes. This article (a) describes the basic anatomy and physiology of the human upper respiratory tract and ocular mucosae, (b) discusses how airborne chemicals induce irritative sensations, and (c) reviews practical means employed for assessing such phenomena, including psychophysical (e.g., threshold and suprathreshold perceptual measures), physiological (e.g., cardiovascular responses), electrophysiological (e.g., event-related potentials), and imaging (e.g., magnetic resonance imaging) techniques. Although traditionally animal models have been used as the first step in assessing such irritation, they are not addressed here since (a) there are numerous reviews available on this topic and (b) many rodents and rabbits are obligate nose breathers whose nasal passages differ considerably from those of humans, potentially limiting generalization of animal-based data to humans. A major goal of this compendium is to inform the reader of procedures for assessing irritation in humans and to provide information of value in the continued interpretation and development of empirical databases upon which future reasoned regulatory health decisions can be made.

Endoscopic marsupialization of congenital nasolacrimal duct cyst with dacryocoele.

A congenital nasolacrimal duct cyst is an uncommon condition in the newborn usually treated by ophthalmologists. Prolapse or expansion of the cyst into the nose may lead to respiratory distress and difficulty in feeding as newborns are obligate nose breathers, which needs the involvement of the Otolaryngologist in diagnosis and management. The authors report a series of 8 children presenting with a congenital nasolacrimal duct cyst and dacryocoele and highlight the importance of endoscopic nasal examination of newborns presenting with respiratory problems. Diagnostic studies included intranasal endoscopy and CT scanning of the nasolacrimal system and nose. All the patients were treated by endoscopic marsupialization of the cyst. Nasolacrimal duct abnormality should be considered in the differential diagnosis of neonatal respiratory distress and nasal obstruction. Nasal endoscopy is essential in the work-up of all children with nasal obstruction and respiratory distress. CT scanning is the investigative method of choice. Endoscopic marsupialization followed by lacrimal duct irrigation is effective in the treatment of congenital nasolacrimal duct cyst and results in complete resolution of symptoms.

L’obstruction nasale néonatale

Neonatal nasal obstruction. J. Leraillez Because neonates are obligate nose breathers, neonatal nasal obstruction may have serious consequences. Prompt diagnosis and appropriate treatment are essential to avoid severe hypoxia. The most common cause of neonatal nasal obstruction is rhinitis. However, it is essential to first rule out anatomical causes such as choanal atresia and stenosis, pyriform aperture stenosis, traumatic deformation or tumors, as these conditions may be life-threatening and require prompt surgical treatment.

ALL NEONATES ARE NOT OBLIGATE NOSE BREATHERS

Unlike adults, neonates are considered obligate nose breathers, hence entirely dependent on a patent nasal airway for ventilation. To fully explore their respiratory response to nasal obstruction, we simultaneously monitored nasal and oral ventilation during sleep and in response to multiple 15 sec nasal occlusions. Ten healthy term infants (mean BW 3600±190g, age 1.7±0.6 d) were studied for 60 min periods. Nasal and oral airflow (via two resistance-matched pneumotachometers), heart rate (HR), TcPO2 PetCO2 and sleep state were continuously recorded.Five of 10 infants initiated and sustained effective oral breathing without arousal during 36±32% of occlusions independent of sleep state. In these infants, arousal occurred during 31±27% of occlusions, and no response in 34±23%. In the remaining 5 infants who did not exhibit oral breathing, arousal occurred in 42±34%, and no response in 58±34% of occlusions. Once begun (within 0-6 sec) oral breathing could be sustained for at least 1 min of continuing nasal occlusion. Tidal vol., resp. rate, HR, TcPO2 and PetCO2 did not change when oral breathing occurred during nasal occlusion, although minute ventilation decreased from 265 to 199 cc/min/kg, p<0.05. Moreover, two of 10 infants exhibited spontaneous combined nasal/oral ventilation while in undisturbed sleep. These results clearly demonstrate that not all infants are obligate nose breathers. Effective oral ventilation can now be included among the neonate's physiologic defenses against life threatening nasal obstruction.

NEW COMPLICATION OF ASSISTED VENTILATION IN THE NEONATE: STRICTURE AFTER NASOTRACHEAL INTUBATION

The purpose of this paper is to report a potentially serious complication of nasotracheal intubation in the neonate, not previously reported. In our nurseries over the last 1½ years, 130 surviving infants received ventilatory support with a Bournes respirator and nasotracheal airway. Primary diagnosis was idiopathic respiratory distress syndrome (IRDS) in 98, meconium aspiration in 9, sepsis in 2, diaphragmatic hernia in 5, apnea in 3, post operative support in 13. Four infants developed unilateral nasal strictures. All weighed less than 1600 grams, were intubated in the first 4 days of life with 3.0 mm or 3.5 mm portex tubes, for duration of intubation 3, 3, 8 and 48 days respectively. Only one tube change was required and that in the 48 day baby. Etiology of the stricture is unknown. Three have been seen in follow up at 4 or 6 months; the involved nasal passageway was patent but very diminished in size. There have been no apparent problems associated with the strictures to date. These findings are particularly important to those using any form of ventilatory support involving both nares because development of bilateral nasal strictures in infants who are obligate nose breathers could potentially be lethal.

SUDDEN UNEXPECTED DEATH (SUD)

To the Editor .—Dr. Shaw's hypothesis that sudden unexpected death in infancy results from obstruction of the nasal airway to obligate nose breathers (Amer J Dis Child 119 :416-418, 1970) is indeed intriguing. It is widely held that phenylephrine nose drops are contraindicated in young infants (less than 6 months of age) due to the rebound mucosal edema which follows their use. It would be interesting to know if any of Dr. Shaw's patients had received phenylephrine nose drops shortly before their death. Certainly if Dr. Shaw's hypothesis is correct, vigorous efforts should be made to warn physicians and parents of the danger of administering decongestant nose drops to young infants. Such a program may lead to a reduction in the mortality due to SUD.