Head-out Body Plethysmography Research Articles

Influence of prenatal nicotine exposure on postnatal development of breathing pattern.

To determine if prenatal nicotine exposure alters the postnatal development of the ventilatory pattern and the frequency and duration of apneas, we recorded respiratory airflow with head-out body plethysmography in awake neonates on postnatal days 1, 2, 6, 10, 14, and 18. Data from 12 nicotine-exposed animals were compared with data from 12 saline-exposed animals. Nicotine (6 mg/kg of nicotine tartrate per day) or saline exposure was induced by osmotic minipumps that were implanted subdermally on the fifth day of gestation in Sprague-Dawley Dams. Although both saline- and nicotine-exposed pups gained weight at the same rate throughout the studies, there were subtle differences in ventilatory indices between the two groups. Nicotine-exposed animals had a significantly higher breathing frequency on day 10, and a lower tidal volume on days 14 and 18. Although ventilation tended to be lower in the nicotine-exposed animals, the difference was not significant. There was a significantly higher frequency of apneas in the nicotine-exposed compared with the saline-exposed animals on postnatal days 1 and 2, but the apnea duration did not differ between the groups. No apneas were observed in any of the animals after the sixth postnatal day. Prenatal nicotine exposure is associated with a greater incidence of apneas on the first two postnatal days, and then an altered breathing pattern that manifests at a later stage of development.

Noninvasive measurement of midexpiratory flow indicates bronchoconstriction in allergic rats

This study was designed to evaluate the value and applicability of tidal breathing pattern analysis to assess bronchoconstriction in conscious rats. Using noninvasive, head-out body plethysmography and the decrease in tidal midexpiratory flow (EF(50)), we measured airway responsiveness (AR) to inhaled acetylcholine and allergen in conscious Brown-Norway rats, followed by invasive determination of pulmonary conductance (GL) and EF(50) in anesthetized rats. Dose-response studies to acetylcholine showed that noninvasively recorded EF(50) closely reflected the dose-dependent decreases observed with the invasive monitoring of simultaneously measured GL and EF(50). After sensitization and intratracheal boost to ovalbumin or saline, rats were assessed for early and late AR to aerosolized ovalbumin. Ovalbumin aerosol challenge resulted in early and late AR in allergen-sensitized rats, whereas controls were unresponsive. The allergen-specific AR, as measured noninvasively by EF(50), was similar in degree compared with invasively recorded EF(50) and GL and was associated with enhanced IgE and airway inflammation. We conclude that EF(50) is a noninvasive and physiologically valid index of bronchoconstriction in a rat model of asthma.

Tidal midexpiratory flow as a measure of airway hyperresponsiveness in allergic mice.

A method for the noninvasive measurement of airway responsiveness was validated in allergic BALB/c mice. With head-out body plethysmography and the decrease in tidal midexpiratory flow (EF(50)) as an indicator of airway obstruction, responses to inhaled methacholine (MCh) and the allergen ovalbumin were measured in conscious mice. Allergen-sensitized and -challenged mice developed airway hyperresponsiveness as measured by EF(50) to aerosolized MCh compared with that in control animals. This response was associated with increased allergen-specific IgE and IgG1 production, increased levels of interleukin-4 and interleukin-5 in bronchoalveolar lavage fluid and eosinophilic lung inflammation. Ovalbumin aerosol challenge elicited no acute bronchoconstriction but resulted in a significant decline in EF(50) baseline values 24 h after challenge in allergic mice. The decline in EF(50) to MCh challenge correlated closely with simultaneous decreases in pulmonary conductance and dynamic compliance. The decrease in EF(50) was partly inhibited by pretreatment with the inhaled beta(2)-agonist salbutamol. We conclude that measurement of EF(50) to inhaled bronchoconstrictors by head-out body plethysmography is a valid measure of airway hyperresponsiveness in mice.

Sequential Development of Airway Hyperresponsiveness and Acute Airway Obstruction in a Mouse Model of Allergic Inflammation

Background: Mouse models have been established mirroring key features of human bronchial asthma including airway hyperresponsiveness (AHR). Acute airway obstruction in response to an allergen challenge, however, remains to be demonstrated in these models. Objective: A mouse model of allergic lung inflammation was employed to analyze the development of specific (allergen-induced) and nonspecific (methacholine-induced) airway obstruction. Methods: Mice were sensitized to ovalbumin (OVA) and challenged with OVA aerosol twice each week during four weeks. Changes in lung functions were determined by noninvasive head-out body plethysmography. The development of acute airway obstruction after OVA challenge and AHR after methacholine aerosol application were assessed by a decrease in the mid-expiratory flow rate (EF₅₀). Results: Two airway challenges were sufficient to induce AHR (5.7 vs. 15 mg/ml methacholine). Further OVA challenges reduced the baseline EF₅₀ from 1.85 to 1.20 ml/s (4th week) and induced acute airway obstruction. The OVA-induced obstruction was maximal in the 4th week (EF₅₀ = 0.91 ml/s). Conclusion: The development of acute airway obstruction in allergen-sensitized mice was demonstrated by means of head-out body plethysmography. In our model, AHR was observed before the development of airway obstruction.

An improved method for airway assessment in children

Respiratory mode determination using the simultaneous nasal and oral respirometric technique (SNORT) or a head-out body plethysmography can be time-consuming, expensive, and intimidating to children. We have developed an improved method for assessing respiratory mode that uses inductive plethysmography linked to a menu-driven computer program that circumvents some of these problems. An assessment of 29 subjects over as many as nine separate time points suggests that respiratory mode measurements remain fairly uniform in some children, but can vary significantly in others.

Nasal polyps: Effects of seasonal allergen exposure

Nasal polyps are characterized by chronic eosinophilic inflammation and often coexist with rhinitis and asthma. Many patients with polyps have no detectable allergy, and it is considered that allergy, at least in many cases, is not relevant to polyp pathogenesis. To explore the association of nasal polyps with allergy, 16 patients with polyps and ragweed allergy (PRW +) and 16 patients with polyps who were not allergic to ragweed (PRW -) were compared with patients without polyps, 16 who were allergic to ragweed (NPRW +) and 16 who were not allergic to ragweed (NPRW -), before and during the ragweed season. The level of ragweed allergy was comparable in the PRW + and NPRW + populations as determined by ragweed skin test wheal diameter, ragweed IgE RAST percent binding, and total serum IgE. Symptom scores before the ragweed season recorded on visual analog scales for the symptoms of blockage, sneezing, decreased smell, itch, postnasal drip, and runny nose were high in patients in the PRW + and PRW - groups and did not change during ragweed season. Mean symptom scores were low in the NPRW + group before ragweed season and increased during the season to levels similar to those of patients in the PRW + and PRW - groups. Preseason nasal lavage albumin concentration was higher in subjects with polyps than those without polyps (58.5, 98) versus (13.6, 15 μg/ml) ( p = 0.02) and did not change significantly in any group with seasonal exposure. Data are presented as mean, 1 SD; comparisons are made with unpaired t tests. The preseason percent eosinophils in the nasal irrigation fluid was higher in the subjects with polyps than in subjects without polyps (18, 25) versus (0.9, 2%), ( p = 0.0002) and changed little for patients in the PRW + group during ragweed season. In the NPRW + group the percent eosinophils increased greatly from low preseason counts, (comparison made with paired t test) (2.2%) to 28, 33% ( p = 0.02), the latter comparable to those of subjects with polyps. The nasal lavage eosinophil cationic protein concentration out of season was higher in subjects with polyps than in those without polyps (9.7, 10) versus (1.4, 1.0) ( p = 0.0001) and did not change in subjects with polyps during seasonal exposure. Nasal resistance was measured by head-out body plethysmography. It was slightly higher in subjects with polyps than in those without polyps out of season. In conclusion, highly ragweed-allergic patients with polyps had symptoms and elevated markers of nasal mucosal inflammation (percent eosinophils and eosinophil cationic protein and albumin concentrations) out of season, and these did not increase in relation to natural seasonal allergen exposure. Ragweed allergic subjects with no polyps had large seasonal increases in symptoms and nasal irrigation fluid percent eosinophils. We conclude that ongoing conditions, perhaps nasal airway mucosal inflammation, in nasal polyposis may lead to a loss of susceptibility to potential additional effects of inhaled allergen. (J A LLERGY C LIN I MMUNOL 1994;93:567-74.)

Dynamic mechanisms determine functional residual capacity in mice, Mus musculus.

Awake mice (22.6--32.6 g) were anesthetized intravenously during head-out body plethysmography. One minute after pentobarbital sodium anesthesia, tidal volume had fallen from 0.28 +/- 0.04 to 0.14 +/- 0.02 ml and frequency from 181 +/- 20 to 142 +/- 8. Functional residual capacity (FRC) decreased by 0.10 +/- 0.02 ml. Expiratory flow-volume curves were linear, highly repeatable, and submaximal over substantial portions of expiration in awake and anesthetized mice; and expiration was interrupted at substantial flows that abruptly fell to and crossed zero as inspiration interrupted relaxed expiration. FRC is maintained at a higher level in awake mice due to a higher tidal volume and frequency coupled with expiratory braking (persistent inspiratory muscle activity or increased glottal resistance). In anesthetized mice, the absence of braking, coupled with reductions in tidal volume and frequency and a prolonged expiratory period, leads to FRCs that approach relaxation volume (Vr). An equation in derived to express the difference between FRC and Vr in terms of the portion of tidal volume expired without braking, the slope of the linear portion of the expiratory flow-volume curve expressed as V/V, the time fraction of one respiratory cycle spent in unbraked expiration, and respiratory frequency.