Total Respiratory System Resistance Research Articles

Para-Cyclists Present Impaired Lung Function and Mechanics Independent of Peripheral and Respiratory Muscle Strength

Objective: The present study investigated the possible changes in respiratory function and mechanics in paralympic cyclists in comparison with cyclists. Design: Lung function (spirometry) and mechanics (impulse oscillometry) pre- and post-bronchodilator, the levels of FeNO and the peripheral and respiratory muscle strength were evaluated in paralympic cyclists [spinal injury from C5 (incomplete injury) until T11 (complete injury); (n=8)] and cyclists (n=12). Results: Paralympic cyclists presented reduced FVC, FEV1, PEF, VC In and MEF75%. Of note, only athletes presented response to bronchodilator, as observed for FEV and for FVC/FEV1. Respiratory impedance (Z5Hz), total respiratory system resistance (R5Hz) was impaired in paralympic cyclists. No differences were found hand grip and respiratory muscle strength and for FeNO comparing paralympic cyclists with cyclists. Conclusion: We conclude that para-cyclists present impaired lung function and mechanics and that such impairments are not correlated with reduction in the respiratory or peripheral muscle strength or with pulmonary inflammation.

Mechanical effects of obesity on central and peripheral airway resistance in nonasthmatic early pubescent children.

In children, obesity typically reduces functional residual capacity (FRC), which reduces airway caliber and increases airway resistance. Whether these obesity-related changes in respiratory function can alter bronchodilator responsiveness is unknown. To investigate bronchodilator responsiveness in nonasthmatic children with and without obesity. Seventy nonasthmatic children, 8-12 years old, without (n = 19) and with (n = 51) obesity, completed spirometry, impulse oscillometry, and airway resistance measurements through plethysmography pre/post 360 µg of inhaled albuterol. FRC was assessed pre albuterol. A two-way analysis of variance determined the effects of obesity (group) and inhaled albuterol (pre-post) on outcome measures. FRC (%total lung capacity) was 16% lower in children with obesity compared with those without obesity. There was no significant group by pre-post albuterol interaction on any outcome variables. Albuterol inhalation reduced total, central and peripheral airway resistance and increased airway reactance (i.e., less negative) to a similar degree in children with and without obesity. In children with obesity, airway resistance was increased whether measured by impulse oscillometry or plethysmography. However, once airway resistance was adjusted for lung volumes (i.e., specific airway resistance or sRaw ), there were no differences between children with and without obesity. In addition, significant but moderate associations were detected between chest mass and FRC (r = -0.566; p < 0.001), FRC and total airway resistance (i.e., Raw ; r = -0.445; p < 0.001). In nonasthmatic early pubescent children, obesity increases total, central, and peripheral respiratory system resistance. However, the added respiratory system resistance and low lung volume breathing with obesity are not sufficient to reduce bronchodilator responsiveness.

Exogenous leptin enhances markers of airway fibrosis in a mouse model of chronic allergic airways disease

BackgroundAsthma patients with comorbid obesity exhibit increased disease severity, in part, due to airway remodeling, which is also observed in mouse models of asthma and obesity. A mediator of remodeling that is increased in obesity is leptin. We hypothesized that in a mouse model of allergic airways disease, mice receiving exogenous leptin would display increased airway inflammation and fibrosis.MethodsFive-week-old male and female C57BL/6J mice were challenged with intranasal house dust mite (HDM) allergen or saline 5 days per week for 6 weeks (n = 6–9 per sex, per group). Following each HDM exposure, mice received subcutaneous recombinant human leptin or saline. At 48 h after the final HDM challenge, lung mechanics were evaluated and the mice were sacrificed. Bronchoalveolar lavage was performed and differential cell counts were determined. Lung tissue was stained with Masson’s trichrome, periodic acid-Schiff, and hematoxylin and eosin stains. Mouse lung fibroblasts were cultured, and whole lung mRNA was isolated.ResultsLeptin did not affect mouse body weight, but HDM+leptin increased baseline blood glucose. In mixed-sex groups, leptin increased mouse lung fibroblast invasiveness and increased lung Col1a1 mRNA expression. Total lung resistance and tissue damping were increased with HDM+leptin treatment, but not leptin or HDM alone. Female mice exhibited enhanced airway responsiveness to methacholine with HDM+leptin treatment, while leptin alone decreased total respiratory system resistance in male mice.ConclusionsIn HDM-induced allergic airways disease, administration of exogenous leptin to mice enhanced lung resistance and increased markers of fibrosis, with differing effects between males and females.

A portable fan-based device for evaluating lung function in horses by the forced oscillation technique

Objective. The assessment of lung mechanics in horses is nowadays based on invasive methods that may require sedation. The forced oscillation technique (FOT) allows the non-invasive assessment of respiratory mechanics during spontaneous breathing, but current devices are complex, cumbersome, expensive, and difficult to be applied in horses. Approach. We developed a portable FOT device based on a novel approach in which the pressure waveforms are generated by a servo-controlled ducted fan. This new approach allows the design of devices that are more sturdy, compact, and portable compared to already existing approaches. The prototype includes 1) a small microcontroller-based electronic board for controlling the fan and measuring flow and pressure and 2) an optimized data processing algorithm. Main results. This device provides a maximum error of 0.06 cmH2O·s/L and 0.15 cmH2O·s/L in measuring respiratory resistance and reactance during in-vitro validation. A pilot study was also performed on three healthy horses and three horses with severe equine asthma (SEA) and it demonstrated good tolerability and feasibility of the new device. Total respiratory system resistance (R rs) and reactance (X rs) significantly differed (p < 0.05) between groups. At 5 Hz, R rs was 0.66 ± 0.02 cmH2O·s/L and 0.94 ± 0.07 cmH2O·s/L in healthy and in SEA, respectively. X rs 0.38 ± 0.02 cmH2O·s/L and −0.27 ± 0.05 cmH2O·s/L. Significance. This novel approach for applying FOT allowed the development of a small, affordable, and portable device for the non-invasive evaluation of respiratory mechanics in spontaneously breathing horses, providing a useful new tool for improving veterinary respiratory medicine. Moreover, our results provide supporting evidence of the value of this novel approach for developing portable FOT devices also for applications in humans.

Evaluation of Lung Aeration and Respiratory System Mechanics in Obese Dogs Ventilated With Tidal Volumes Based on Ideal vs. Current Body Weight.

We describe the respiratory mechanics and lung aeration in anesthetized obese dogs ventilated with tidal volumes (VT) based on ideal (VTi) vs. current (VTc) body weight. Six dogs with body condition scores ≥ 8/9 were included. End-expiratory respiratory mechanics and end-expiratory CT-scan were obtained at baseline for each dog. Thereafter, dogs were ventilated with VT 15 ml kg−1 based on VTi and VTc, applied randomly. Respiratory mechanics and CT-scan were repeated at end-inspiration during VTi and VTc. Data analyzed with linear mixed models and reported as mean ± SD or median [range]. Statistical significance p < 0.05. The elastance of the lung, chest wall and respiratory system indexed by ideal body weight (IBW) were positively correlated with body fat percentage, whereas the functional residual capacity indexed by IBW was negatively correlated with body fat percentage. At end-expiration, aeration (%) was: hyperaeration 0.03 [0.00–3.35], normoaeration 69.7 [44.6–82.2], hypoaeration 29.3 [13.6–49.4] and nonaeration (1.06% [0.37–6.02]). Next to the diaphragm, normoaeration dropped to 12 ± 11% and hypoaeration increased to 90 ± 8%. No differences in aeration between groups were found at end-inspiration. Airway driving pressure (cm H2O) was higher (p = 0.002) during VTc (9.8 ± 0.7) compared with VTi (7.6 ± 0.4). Lung strain was higher (p = 0.014) during VTc (55 ± 21%) than VTi (38 ± 10%). The stress index was higher (p = 0.012) during VTc (SI = 1.07 [0.14]) compared with VTi (SI = 0.93 [0.18]). This study indicates that body fat percentage influences the magnitude of lung, chest wall, and total respiratory system elastance and resistance, as well as functional residual capacity. Further, these results indicate that obese dogs have extensive areas of hypoaerated lungs, especially in caudodorsal regions. Finally, lung strain and airway driving pressure, surrogates of lung deformation, are higher during VTc than during VTi, suggesting that in obese anesthetized dogs, ventilation protocols based on IBW may be advantageous.

Single-Cell RNA Sequencing Reveals a Unique Monocyte Population in Bronchoalveolar Lavage Cells of Mice Challenged With Afghanistan Particulate Matter and Allergen.

Upon returning from deployment to Afghanistan, a substantial number of U.S. military personnel report deployment-related lung disease (DRLD) symptoms, including those consistent with an asthma-like airways disease. DRLD is thought to be caused by prolonged inhalation of toxic desert particulate matter, which can persist in the postdeployment setting such as exposure to common household allergens. The goal of this study was to define the transcriptomic responses of lung leukocytes of mice exposed to Afghanistan desert particulate matter (APM) and house dust mite (HDM). C57BL/6 mice (n = 15/group) were exposed to filtered air or aerosolized APM for 12 days, followed by intranasal PBS or HDM allergen challenges for 24 h. Bronchoalveolar lavage (BAL) cells were collected for single-cell RNA sequencing (scRNAseq), and assessment of inflammation and airway hyper-responsiveness. Unsupervised clustering of BAL cell scRNAseq data revealed a unique monocyte population induced only by both APM and allergen treatments. This population of monocytes is characterized by the expression of genes involved in allergic asthma, including Alox15. We validated Alox15 expression in monocytes via immunostaining of lung tissue. APM pre-exposure, followed by the HDM challenge, led to significantly increased total respiratory system resistance compared with filtered air controls. Using this mouse model to mimic DRLD, we demonstrated that inhalation of airborne PM during deployment may prime airways to be more responsive to allergen exposure after returning home, which may be linked to dysregulated immune responses such as induction of a unique lung monocyte population.

Effects of allergic airway inflammation and chronic intermittent hypoxia on systemic blood pressure.

Asthma and obstructive sleep apnea (OSA) are highly prevalent chronic conditions, and both are associated with systemic hypertension. Additionally, asthma and OSA reciprocally interact, mutually exacerbating each other. In this study, we tested the effect of allergen-induced lower airway inflammation and concurrent chronic intermittent hypoxia (CIH) on systemic blood pressure (BP), pulmonary function, and proinflammatory cytokines, in a rat model. Brown Norway rats were exposed to 43 days of normoxia (NORM) or CIH, concurrent with weekly house dust mite (HDM) challenges. BP was measured 1 day after the last HDM challenge. On day 44, pulmonary function was tested, and blood for Th-2 and Th-1 cytokine levels was collected. HDM significantly increased mean (P = 0.002), systolic (P = 0.003), and diastolic (P = 0.004) BP compared with saline-challenged controls. Higher mean BP significantly correlated to increased total respiratory system resistance (R2 = 0.266, P = 0.002), driven by an association with parenchymal tissue dampening (R2 = 0.166, P = 0.016). HDM relative to saline-challenged controls increased the expression of serum IL-6 (P = 0.008), but no relationships of systemic BP with IL-6 or any other cytokines were found. CIH did not alter the allergen-induced responses on BP, although it tended to increase the expression of serum IL-6 (P = 0.06) and monocyte chemoattractant protein-1 (MCP-1, P = 0.09), regardless of HDM challenge. Chronic allergen-induced airway inflammation results in systemic hypertension that is correlated to the degree of distal airway obstruction induced by the allergen. These effects do not appear to be explained by the associated systemic inflammation.

Environmental Tobacco Smoke Affects Lung Function of Preschoolers With Asthma Even After a Decade

To evaluate whether early tobacco smoke exposure has a long-term effect on lung function.Children (n = 105; mean age: 5.62 years) with a history of wheeze and bronchodilator response had been previously enrolled for a study evaluating the association between maternal smoking and preschool asthma. Children could not have taken corticosteroids in the previous 6 months nor have had a respiratory tract infection in the previous 2 weeks. These children were evaluated at a follow-up visit 10 years after the initial enrollment (n = 64; mean age: 14.22 years).The cohort in this study had been assessed at enrollment for environmental tobacco smoke exposure by urinary cotinine and questionnaires. At both enrollment and the 10-year follow-up, fractional exhaled nitric oxide (FeNO), impulse oscillometry (IOS), blood eosinophil counts, and allergic sensitization to indoor and outdoor aeroallergens were assessed. At the 10-year follow-up, children also performed spirometry and a methacholine challenge. Results were compared between enrollment and follow-up.At the 10-year follow-up, fewer children wheezed in the previous year (11% vs 83%), whereas more children had positive allergy testing results (92% vs 70%). Blood eosinophil count, FeNO, and total respiratory system resistance (resistance at 5 Hz [R5]), one of the IOS indices, were all decreased at follow-up. Forty-three percent of parents stopped smoking during the 10 years. Approximately one-third of children reported asthma symptoms and the need for asthma medications in the previous 2 months at the follow-up visit. None reported smoking. Being overweight correlated with forced expiratory volume in 1 second and/or forced vital capacity and the IOS indices (R5 and area under reactance), at the follow-up visit but did not correlate with the preschool urinary cotinine levels. However, preschool urinary cotinine levels did significantly correlate with increased FeNO scores, blood eosinophils, and R5 and decreased reactance (by 5) at the follow-up. No significant correlation was seen with forced expiratory volume in 1 second or methacholine challenge.Early tobacco smoke exposure is linked to the presence of airway inflammation and decreased lung function in older children with a history of asthma.Limitations included the lack of a control asthma group without preschool exposure to tobacco smoke, the small sample size, and lack of interval assessment during the 10-year period to evaluate the potential confounding effect of other environmental factors, socioeconomic factors, or the development of other comorbidities. The study also did not consider whether aeroallergen sensitization had an impact on lung function over time. IOS is not as commonly performed as spirometry for the assessment of asthma, so the use of IOS in assessing and managing asthma in a clinical practice needs further validation. Nevertheless, this study provides further proof that early exposure to tobacco smoke in childhood potentially has long-term negative health effects.

2592. Lung Function as an Indicator of Vaccine Enhanced RSV Disease in Cotton Rats

BackgroundRespiratory syncytial virus (RSV) infection is the leading cause of lower respiratory tract infections in infants and young children. Seronegative children previously vaccinated with formalin-inactivated live RSV formulated with aluminum (FIRSV) developed vaccine enhanced RSV disease (VERD), which is characterized by fever, wheezing, bronchopneumonia, and airway hyperresponsiveness (AHR). We investigated whether impaired lung function can serve as a marker for VERD in an animal model of RSV infection.MethodsUninfected and RSV-infected cotton rats intranasally challenged with 106 pfu of RSV A2 were anesthetized with pentobarbital and tracheostomized. A cannula was placed in the trachea and animals were connected to flexiVent™ (Scireq), which is a computer-controlled piston ventilator that analyzes pressure and volume signals in response to an oscillatory waveform applied at the animal’s airways. Vecuronium bromide was administered to ventilated animals to prevent independent breathing. To measure AHR, animals were exposed to increasing doses of inhaled methacholine, and methacholine-induced bronchoconstriction was measured.ResultsTwo independent studies showed that RSV-infected cotton rats (n = 4) exhibited increased total respiratory system resistance (Rrs) and airway resistance (Rn) following methacholine challenge on days 4 and 6 post-infection compared with uninfected cotton rats (n = 4).ConclusionRSV-induced impairment in lung function can be exploited for the development of a more robust and objective method for assessing vaccine safety in a cotton rat model of respiratory disease compared with traditional histopathological analysis.Disclosures All authors: No reported disclosures.

Effects of Repeated Pulmonary Exposure to Carbon Nanotubes on Lung function

The development of nanotechnology has increased the risk of exposure to types of particles other than combustion-derived ones in the environment, namely, industrial nanomaterials. However, their health impacts have not been fully elucidated yet. This study examined the effects of pulmonary exposure to two types of carbon nanotube (single-walled carbon nanotubes: SWCNT, and multi-walled carbon nanotube: MWCNT) on lung physiology in mice. ICR mice were divided into three experimental groups to repeatedly administer vehicle, SWCNT (50 μg/animal), or MWCNT through intratracheal route; thereafter lung function was examined. The values of total respiratory system resistance (R: P<0.05), elastance (E), Newtonian resistance (Rn), tissue damping (G: P<0.05), and tissue elastance (H) were higher and the value of compliance (C) was lower in the SWCNT group than in the vehicle group. On the other hand, MWCNT tended to augment the values. Taken together, CNT themselves inhaled, can impair airway function.

Acute Effects of Oscillatory PEP and Thoracic Compression on Secretion Removal and Impedance of the Respiratory System in Non-Cystic Fibrosis Bronchiectasis.

Bronchiectasis is characterized by abnormal and permanent dilatation of the bronchi, caused mainly by the progression of inflammatory processes and loss of the ability to remove mucus. Techniques to clear the airways are essential for the treatment of these patients. In this study, we aimed to evaluate the acute effects of oscillatory PEP and thoracic compression on both the clearance of secretions and impedance of airways in subjects with bronchiectasis. This was a randomized crossover single-blinded study that involved both subjects with bronchiectasis and healthy subjects evaluated by using an impulse oscillometry system, which assessed resistance at 5 Hz and resistance 20 Hz, reactance at 5 Hz, reactance area, and resonant frequency, before, after, and 30 min after oscillatory PEP, chest compression, or control sessions. Dry and total weights, adhesiveness, purulence of the expectorated secretions, the dyspnea scale score, the acceptability and tolerance scale score, pulse oximetry, and difficulty in expectoration were also assessed. The dry and total weights of secretions were higher after the use of the oscillatory PEP technique than those in a control session (P = .005 and P = .039, respectively). In the bronchiectasis group, there was a decrease after oscillatory PEP in total airway resistance (P = .04), peripheral resistance (P = .005), and reactance area (P = .001). After compression, there was a decrease in peripheral resistance Hz (P = .001) and reactance area (P = .001). In the healthy group, there was an increase in resistance at 5 Hz (P = .02) after oscillatory PEP. There were no differences in acceptability and tolerance, dyspnea, and oxygen saturation. The oscillatory PEP technique was effective for the removal of secretions and in decreasing total and peripheral respiratory system resistance; thoracic compression had comparable positive effects on the peripheral resistance. Both techniques were safe and well tolerated by the subjects with bronchiectasis. ClinicalTrials.gov registration NCT02509637.).

Respiratory mechanics of patients with morbid obesity.

ABSTRACTObjectiveTo evaluate the different components of the resistance of the respiratory system, respiratory muscle strength and to investigate the occurrence of expiratory flow limitation (EFL) in patients with morbid obesity (MO) when seated.MethodsThe sample was composed of MO (BMI≥40 kg/m2) and non-obese individuals (NO) with a BMI between 18 and 30 kg/m2. The protocol consisted of the anthropometric assessment and the following measures of respiratory function: spirometry, maximal inspiratory and expiratory pressures (MIP and MEP, respectively) and impulse oscillometry. The group comparison was performed using T-test for unpaired samples. The correlations were evaluated by the Pearson test with a significance level of 5%.ResultsFifty MO (age 40±10.4 years, 1.64±0.09 m, 138.8±33.6 kg and 50.7±8.9 kg/m2), and 30 NO (age 37.6±11.5 years, 1.67±0.09 m, 65.2±10.3 kg and 23.2±22 kg/m2) were evaluated. The MO showed higher values of total, peripheral, airways, tissue and central resistance when compared to the NO. No patient showed EFL. The waist circumference was associated with spirometric variables, MIP, and MEP. The waist-to-hip ratio was correlated to respiratory mechanics and spirometric variables, MIP, and MEP. ConclusionMorbidly obese patients with no obstructive spirometric pattern show increased total, airway, peripheral, and tissue respiratory system resistance when compared to nonobese. These individuals, however, do not present with expiratory flow limitation and reduced respiratory muscles strength.

Impact of positive end expiratory pressure on cerebral hemodynamic in paediatric patients with post-traumatic brain swelling treated by surgical decompression

IntroductionThe objective of our present study is to evaluate the impact of different PEEP levels on cerebral hemodynamic, gas exchanges and respiratory system mechanics in paediatric patients with post-traumatic brain swelling treated with decompressive craniectomy (DC).Materials and methodsA prospective physiologic study was carried out on 14 paediatric patients presenting with severe traumatic brain swelling treated with DC. Transcranial Doppler ultrasonography was performed on the middle cerebral artery bilaterally after DC. After assessment at ZEEP, intracranial pressure (ICP), cerebral perfusion pressure (CPP), mean arterial pressure (MAP), central venous pressure (CVP) and gas exchanges were recorded at PEEP 4 and PEEP 8.ResultsFrom ZEEP to PEEP 8, the compliance of respiratory system indexed to the weight of the patient significantly increased (P = 0.02) without ICP modifications. No significant variation of the MAP, CPP, Vmed, the total resistance of respiratory system and ohmic resistance of the respiratory system indexed to the weight of the patients was observed. CVP significantly increased between ZEEP and PEEP 8 (P = 0.005), and between PEEP 4 and PEEP 8 (P = 0.05).ConclusionsPEEP values up to 8 cmH20 seem to be safe in paediatric patients with a severe post-traumatic brain swelling treated with DC.

Measurement duration impacts variability but not impedance measured by the forced oscillation technique in healthy, asthma and COPD subjects.

The forced oscillation technique (FOT) is gaining clinical acceptance, facilitated by more commercial devices and clinical data. However, the effects of variations in testing protocols used in FOT data acquisition are unknown. We describe the effect of duration of data acquisition on FOT results in subjects with asthma, chronic obstructive pulmonary disease (COPD) and healthy controls.FOT data were acquired from 20 healthy, 22 asthmatic and 18 COPD subjects for 60 s in triplicate. The first 16, 30 and 60 s of each measurement were analysed to obtain total, inspiratory and expiratory resistance of respiratory system (Rrs) and respiratory system reactance (Xrs) at 5 and 19 Hz.With increasing duration, there was a decrease in total and expiratory Rrs for healthy controls, total and inspiratory Rrs for asthmatic subjects and magnitude of total and inspiratory Xrs for COPD subjects at 5 Hz. These decreases were small compared to the differences between clinical groups. Measuring for 16, 30 and 60 s provided ≥3 acceptable breaths in at least 90, 95 and 100% of subjects, respectively. The coefficient of variation for total Rrs and Xrs also decreased with duration. Similar results were found for Rrs and Xrs at 19 Hz.FOT results are statistically, but likely minimally, impacted by acquisition duration in healthy, asthmatic or COPD subjects.

Pulmonary function, CT and echocardiographic abnormalities in sickle cell disease

ObjectivesTo test the hypothesis that vascular abnormalities on high-resolution CT (HRCT) would be associated with echocardiographic changes and lung function abnormalities in patients with sickle cell disease (SCD) and the...

Comparison Study of Airway Reactivity Outcomes due to a Pharmacologic Challenge Test: Impulse Oscillometry versus Least Mean Squared Analysis Techniques

The technique of measuring transpulmonary pressure and respiratory airflow with manometry and pneumotachography using the least mean squared analysis (LMS) has been used broadly in both preclinical and clinical settings for the evaluation of neonatal respiratory function during tidal volume breathing for lung tissue and airway frictional mechanical properties measurements. Whereas the technique of measuring respiratory function using the impulse oscillation technique (IOS) involves the assessment of the relationship between pressure and flow using an impulse signal with a range of frequencies, requires less cooperation and provides more information on total respiratory system resistance (chest wall, lung tissue, and airways). The present study represents a preclinical animal study to determine whether these respiratory function techniques (LMS and IOS) are comparable in detecting changes in respiratory resistance derived from a direct pharmacological challenge.

Does Decline of Lung Function in Wheezy Infants Justify the Early Start of Controller Medications?

To compare lung function in wheezy infants, with risk factors of asthma and with some immunological parameters which may be useful as predictors of subsequent asthma. The data of 241 infants aged 5–36 mo, with recurrent wheeze (≥3 episodes of physician confirmed wheeze) prior to receiving inhaled corticosteroids or anti-leukotrine agents was retrospectively analyzed. They were subdivided into 2 subgroups; those with asthma risk factors (132 patients) and those without (109 patients) Also, 67 healthy, age and sex matched children without recurrent wheezes were taken as control group. Total serum IgE, eosinophilic percentage, tPTEF/tE (time to peak expiratory flow to total expiratory time), total respiratory system compliance (Crs) and resistance of the respiratory system (Rrs) was done for patients and control groups. Wheezy infants had a significantly higher eosinophilic percentage and total serum IgE as well as a significantly lower pulmonary function parameters when compared to healthy controls. Wheezy infants with positive family history of asthma and those who had not been breast fed showed significant reduction in the mean values of tPTEF/tE and increased both eosinophilic percentage and total serum IgE. Crs was significantly decreased in wheezy infants with positive seasonal variations and those who had increased both eosinophilic percentage and total serum IgE. Rrs showed significant increase in wheezy infants with positive family history of atopy and those who had increased eosinophilic percentage and increased total serum IgE. Lung function, eosinophilic percentage, total serum IgE and asthma risk factors could be used as predictors for ongoing wheeze in this subset of children.

Lung function changes following methacholine inhalation in COPD

The non-specific bronchial hyper-responsiveness reported in mild to moderate COPD is usually attributed to reduced airway calibre accentuating the effect of airway smooth muscle shortening. We hypothesized that in more severe COPD the fall in forced expiratory volume in 1 second (FEV(1)) seen during methacholine challenge would result from an increase in residual volume and decrease in vital capacity rather than an increase in airways resistance. Twenty-five subjects with moderate to severe COPD and 10 asthmatic subjects had spirometry and oscillatory mechanics measured before methacholine challenge and at a 20% fall from baseline post challenge (PC(20)FEV(1)). In the COPD subjects median PC(20) was 0.35mg/mL. Comparing baseline to PC(20) there were significant falls in forced vital capacity (FVC) (2.91 vs. 2.2L; p<0.001), slow vital capacity (3.22 vs. 2.58L; p<0.001) and IC (2.21 vs. 1.75L; p<0.001) without change in FEV(1)/FVC ratio (0.52 vs. 0.52; not significant) or in total lung capacity where this was measured. Total respiratory system resistance (R(5)) was unchanged (0.66 vs. 0.68; not significant) but total respiratory system reactance decreased significantly (-0.33 vs. -0.44; p<0.001). In contrast, the asthmatics became more obstructed and showed a proportionally smaller fall in lung volume with increase in R(5) (0.43 vs. 0.64; p<0.01). In moderate to severe COPD the fall in FEV(1) with methacholine is mainly due to increases in residual volume, which may represent airway closure and new-onset expiratory flow limitation.

Thoracic percussion yields reversible mechanical changes in healthy subjects

In order to characterize the mechanical effects of thoracic percussion per se in lung parenchyma, we analyzed respiratory impedance parameters by impulse oscillometry (12 healthy subjects) and lung mechanics by the least square method (6 healthy subjects) before (PRE-TP) and after (POS-TP) thoracic percussion, and after a deep-breath-maneuver (POS-DB). Pulmonary resistance was similar among PRE-TP, POS-TP and POS-DB while pulmonary dynamic compliance showed a significant reduction after TP (mean +/- SEM: from 0.15 +/- 0.018 L/cmH(2)O to 0.12 +/- 0.016 L/cmH(2)O; P = 0.001), returning to basal values (mean +/- SEM: 0.15 +/- 0.021; P = 0.004) after DB. Reactance parameters (AX and f (0)) evaluated by oscillometry increased significantly after TP, returning to previous values after DB. Total impedance (Z5) and respiratory system resistance at 5 Hz (R5) did not differ significantly among experimental conditions. Our data strongly suggest that thoracic percussion can promote changes in respiratory mechanics compatible with lung collapse and/or pneumoconstriction, which are, however, reversible by deep inspirations.

Effects of Nanoparticles on Lung Physiology in the Presence or Absence of Antigen

Ambient particulate matter (PM) exacerbates allergic airway diseases. Our previous study showed that diesel exhaust particles, the main constituents in urban PM, enhance airway hyperresponsivness in mice. In addition, health effects of PM with a diameter of less than 100 nm, called nanoparticles, have been reported, and we have also demonstrated that carbon nanoparticles exacerbate antigen-related airway inflammation. The present study investigates the effects of pulmonary exposure to two sizes of carbon nanoparticles on lung physiology and lung expression of Muc5ac in the presence or absence of antigen in mice. Nanoparticles alone or ovalbumin (OVA) alone moderately enhanced cholinergic airway reactivity, as assessed by total respiratory system resistance (R) and Newtonian resistance (Rn). In the nanoparticle + OVA groups, all the parameters for lung responsiveness, such as R, compliance, elastance, Rn, tissue damping, and tissue elastance, were worse than those in the vehicle group, the corresponding nanoparticle groups or the OVA group. The lung mRNA level for Muc5ac was significantly higher in the OVA group than in the vehicle group, and further increased in the nanoparticle + OVA groups than in the OVA or the nanoparticle groups. These data suggest that carbon nanoparticles can enhance lung hyperresponsiveness, especially in the presence of antigen. The effects may be mediated, at least partly, through the enhanced lung expression of Muc5ac.