Measurement Of Airway Resistance Research Articles

The measurement of cough response to bronchoconstriction induced by methacholine inhalation in healthy subjects: An examination using the Astograph method

ABSTRACTBackground: We demonstrated that heightened cough response to bronchoconstriction is a fundamental feature of cough variant asthma (CVA). To evaluate this physiological feature of CVA in daily clinical practice, it is necessary to clarify the cough response to bronchoconstriction in healthy subjects. We evaluated cough response to methacholine (MCh)-induced bronchoconstriction in healthy subjects. A forced oscillometry technique was used to measure airway resistance changes with Mch. Methods: Healthy never-smokers (21 men, 20 women; mean 22.3 ± 3.7 years) participated. None had a >3-week cough history, clinically significant respiratory or cardiovascular disorders, or disorders that might put subjects at risk or influence the study results or the subjects’ ability to participate. Twofold increasing concentrations of Mch chloride diluted in phosphate-buffered saline (0.039 to 160 mg/mL) were inhaled from nebulizers at 1-minute intervals during subjects’ tidal breathing after the baseline respiratory resistance (Rrs) was recorded. Mch inhalation continued until Rrs reached twice the baseline value and forced expiratory volume in 1 second (FEV1) decreased to <90% of baseline value. Spirometry was measured before Mch inhalation and immediately after Rrs had increased twofold. Coughs were counted during and for 30 minutes after Mch inhalation. The cough reflex sensitivity to capsaicin was also examined. Results: The number of coughs was 11.1 ± 14.3 (median, 7.0; range, 0 to 71; reference range, 0 to 39.7). There was no significant difference in the cough response between the sexes. The reproducibility of the cough response to bronchoconstriction was sufficient. No correlation existed between the bronchoconstriction-induced cough response and capsaicin cough-reflex sensitivity. Conclusions: Using the Astograph method, cough response to bronchoconstriction could be measured easily, safely and highly reproducibly in healthy subjects.

Novel analysis of 4DCT imaging quantifies progressive increases in anatomic dead space during mechanical ventilation in mice.

Increased dead space is an important prognostic marker in early acute respiratory distress syndrome (ARDS) that correlates with mortality. The cause of increased dead space in ARDS has largely been attributed to increased alveolar dead space due to ventilation/perfusion mismatching and shunt. We sought to determine whether anatomic dead space also increases in response to mechanical ventilation. Mice received intratracheal lipopolysaccharide (LPS) or saline and mechanical ventilation (MV). Four-dimensional computed tomography (4DCT) scans were performed at onset of MV and after 5 h of MV. Detailed measurements of airway volumes and lung tidal volumes were performed using image analysis software. The forced oscillation technique was used to obtain measures of airway resistance, tissue damping, and tissue elastance. The ratio of airway volumes to total tidal volume increased significantly in response to 5 h of mechanical ventilation, regardless of LPS exposure, and airways demonstrated significant variation in volumes over the respiratory cycle. These findings were associated with an increase in tissue elastance (decreased lung compliance) but without changes in tidal volumes. Airway volumes increased over time with exposure to mechanical ventilation without a concomitant increase in tidal volumes. These findings suggest that anatomic dead space fraction increases progressively with exposure to positive pressure ventilation and may represent a pathological process.NEW & NOTEWORTHY We demonstrate that anatomic dead space ventilation increases significantly over time in mice in response to mechanical ventilation. The novel functional lung-imaging techniques applied here yield sensitive measures of airway volumes that may have wide applications.

Lung Function in Women with Idiopathic Central Precocious Puberty: A Pilot Study

Background: Studies have reported that women with early menarche (≤10 years) have lower lung function. Aim: To investigate lung function in women with a history of idio pathic central precocious puberty (ICPP) treated during childhood with gonadotropin-releasing hormone agonist (GnRHa). Methods: ICPP women (n = 23) were compared with healthy age-matched controls (n = 23). Subjects were clinically evaluated by means of a questionnaire, baseline and post-β<Sub>2</Sub> agonist spirometry, impulse oscillometry (a measure of airway resistance), and measurement of fractional exhaled nitric oxide (FeNO). Results: Patients had lower lung function values than controls: forced expiratory volume in 1 s (FEV<Sub>1</Sub>) (median 97.90 vs. 109.45; p = 0.011), FEV<Sub>1</Sub> after β<Sub>2</Sub> agonist (100.80 vs. 114.10; p = 0.013), peak expiratory flow (92.90 vs. 97.95; p = 0.031), and maximum mid-expiratory flow (MMEF) (80.80 vs. 106.30; p = 0.008). FeNO was significantly lower in the patients (p < 0.001). Significant reversibility of FEV<Sub>1</Sub> after β<Sub>2</Sub> agonist was observed in 8.7% of the patients. FEV<Sub>1</Sub>/forced vital capacity and MMEF after β<Sub>2</Sub> agonist correlated negatively with hysterometry at diagnosis (p = 0.009 and p = 0.03, respectively). There was a negative correlation between age at diagnosis and airway resistance. Conclusions: Women with ICPP seem to have lower lung function despite treatment with GnRHa. Further research on the effects of sex hormones on the airways should take into account potential interplay with factors affecting the start of puberty.

Anti-fibrotic effects of chronic treatment with the selective FXR agonist obeticholic acid in the bleomycin-induced rat model of pulmonary fibrosis

Farnesoid X receptor (FXR) activation by obeticholic acid (OCA) has been demonstrated to inhibit inflammation and fibrosis development in liver, kidney and intestine in multiple disease models. FXR activation has also been demonstrated to suppress the inflammatory response and to promote lung repair after lung injury. This study investigated the protective effects of OCA treatment (3 or 10mg/kg/day) on inflammation, tissue remodeling and fibrosis in the bleomycin-induced pulmonary fibrosis rat model. Effects of OCA treatment on morphological and molecular alterations of the lung, as well as remodeling of the alveoli and the right ventricle were also evaluated. Lung function was assessed by measuring airway resistance to inflation.In the acute phase (7days), bleomycin promoted an initial thickening and fibrosis of the lung interstitium, with upregulation of genes related to epithelial proliferation, tissue remodeling and hypoxia. At 28days, an evident increase in the deposition of collagen in the lungs was observed. This excessive deposition was accompanied by an upregulation of transcripts related to the extracellular matrix (TGFβ1, SNAI1 and SNAI2), indicating lung fibrosis. Administration of OCA protected against bleomycin-induced lung damage by suppressing molecular mechanisms related to epithelial-to-mesenchymal transition (EMT), inflammation and collagen deposition, with a dose-dependent reduction of proinflammatory cytokines such as IL-1β and IL-6, as well as TGF-β1 and SNAI1 expression. Pirfenidone, a recently approved treatment for idiopathic pulmonary fibrosis (IPF), significantly counteracted bleomycin-induced pro-fibrotic genes expression, but did not exert significant effects on IL-1β and IL-6. OCA treatment in bleomycin-challenged rats also improved pulmonary function, by effectively normalizing airway resistance to inflation and lung stiffness in vivo. Results with OCA were similar, or even superior, to those obtained with pirfenidone.In conclusion, our results suggest an important protective effect of OCA against bleomycin-induced lung fibrosis by blunting critical mediators in the pathogenesis of IPF.

Nasal decongestants in monotherapy for the common cold.

Nasal decongestants in monotherapy for the common cold.

Role of IOS in evaluation of patients with interstitial lung diseases

AimIn patients with ILD, a static expiratory pressure–volume curve of the lung is generally shifted downward and rightward and spirometry results reveal reduced vital capacity (Thompson et al., 1989). However, reduced vital capacity may occur even in patients with obstructive lung diseases and in other situations, such as chest wall restriction, lung resection, inspiratory muscle weakness, or poor cooperation with spirometry. In addition, spirometry is sometimes difficult to perform with elderly, cognitively impaired patients, or severe respiratory distress (Kubota et al., 2009). IOS is a simple, noninvasive method requiring only passive patient cooperation that allows for the evaluation of lung function through the measurement of both airway resistance and airway reactance. The aim of this study is to assess the role of IOS in the evaluation of the cases of interstitial lung diseases. MethodologyThis study included 48 patients with interstitial lung diseases of different causes. Pulmonary function test by spirometry was done to measure FEV1, FVC, FEV1/FVC, MEF25-75 and pulmonary function test by impulse oscillometry (IOS). We measured R5, R20, X5, RF. Oxygen saturation and 6MWT. ResultsIn our study 87% were females. The mean age in our study was 50.75±11.1. Mean X5 was low in ILD denoting restrictive pattern, and there was a negative correlation between X5andFEV1/FVC. There was a positive correlation between X5and6MWT. The mean R5 was 150.33±while mean R20 was 108.33±48.66 this is within normal then this is considered an index of mild small airways obstruction.

Exploratory study into the effect of abdominal mass loading on airways resistance and ventilatory failure

ObjectiveWe hypothesised that the airway resistance during tidal breathing would correlate with a particular pattern of increasing obesity, particularly when supine, and would differ between participants with and without ventilatory...

Methods of Airway Resistance Assessment

Airway resistance is the ratio of driving pressure to the rate of the airflow in the airways. The most frequent methods used to measure airway resistance are whole-body plethysmography, the interrupter technique and the forced oscillation technique. All these methods allow to measure resistance during respiration at the level close to tidal volume, they do not require forced breathing manoeuvres or deep breathing during measurement. The most popular method for measuring airway resistance is whole-body plethysmography. The results of plethysmography include among others the following parameters: airway resistance (Raw), airway conductance (Gaw), specific airway resistance (sRaw) and specific airway conductance (sGaw). The interrupter technique is based on the assumption that at the moment of airway occlusion, air pressure in the mouth is equal to the alveolar pressure . In the forced oscillation technique (FOT), airway resistance is calculated basing on the changes in pressure and flow caused by air vibration. The methods for measurement of airway resistance that are described in the present paper seem to be a useful alternative to the most common lung function test — spirometry. The target group in which these methods may be widely used are particularly the patients who are unable to perform spirometry.

Capnographic Parameters in Ventilated Patients: Correspondence with Airway and Lung Tissue Mechanics

Although the mechanical status of the lungs affects the shape of the capnogram, the relations between the capnographic parameters and those reflecting the airway and lung tissue mechanics have not been established in mechanically ventilated patients. We, therefore, set out to characterize how the mechanical properties of the airways and lung tissues modify the indices obtained from the different phases of the time and volumetric capnograms and how the lung mechanical changes are reflected in the altered capnographic parameters after a cardiopulmonary bypass (CPB). Anesthetized, mechanically ventilated patients (n = 101) undergoing heart surgery were studied in a prospective consecutive cross-sectional study under the open-chest condition before and 5 minutes after CPB. Forced oscillation technique was applied to measure airway resistance (Raw), tissue damping (G), and elastance (H). Time and volumetric capnography were performed to assess parameters reflecting the phase II (SII) and phase III slopes (SIII), their transition (D2min), the dead-space indices according to Fowler, Bohr, and Enghoff and the intrapulmonary shunt. Before CPB, SII and D2min exhibited the closest (P = 0.006) associations with H (0.65 and -0.57; P < 0.0001, respectively), whereas SIII correlated most strongly (P < 0.0001) with Raw (r = 0.63; P < 0.0001). CPB induced significant elevations in Raw and G and H (P < 0.0001). These adverse mechanical changes were reflected consistently in SII, SIII, and D2min, with weaker correlations with the dead-space indices (P < 0.0001). The intrapulmonary shunt expressed as the difference between the Enghoff and Bohr dead-space parameters was increased after CPB (95% ± 5% [SEM] vs 143% ± 6%; P < 0.001). In mechanically ventilated patients, the capnographic parameters from the early phase of expiration (SII and D2min) are linked to the pulmonary elastic recoil, whereas the effect of airway patency on SIII dominates over the lung tissue stiffness. However, severe deterioration in lung resistance or elastance affects both capnogram slopes.

Hyperpolarized 3He magnetic resonance imaging ventilation defects in asthma: relationship to airway mechanics.

In patients with asthma, magnetic resonance imaging (MRI) provides direct measurements of regional ventilation heterogeneity, the etiology of which is not well‐understood, nor is the relationship of ventilation abnormalities with lung mechanics. In addition, respiratory resistance and reactance are often abnormal in asthmatics and the frequency dependence of respiratory resistance is thought to reflect ventilation heterogeneity. We acquired MRI ventilation defect maps, forced expiratory volume in one‐second (FEV 1), and airways resistance (Raw) measurements, and used a computational airway model to explore the relationship of ventilation defect percent (VDP) with simulated measurements of respiratory system resistance (Rrs) and reactance (Xrs). MRI ventilation defect maps were experimentally acquired in 25 asthmatics before, during, and after methacholine challenge and these were nonrigidly coregistered to the airway tree model. Using the model coregistered to ventilation defect maps, we narrowed proximal (9th) and distal (14th) generation airways that were spatially related to the MRI ventilation defects. The relationships for VDP with Raw measured using plethysmography (r = 0.79), and model predictions of Rrs>14 (r = 0.91, P < 0.0001) and Rrs>9 (r = 0.88, P < 0.0001) were significantly stronger (P = 0.005; P = 0.03, respectively) than with FEV 1 (r = −0.68, P = 0.0001). The slopes for the relationship of VDP with simulated lung mechanics measurements were different (P < 0.0001); among these, the slope for the VDP‐Xrs0.2 relationship was largest, suggesting that VDP was dominated by peripheral airway heterogeneity in these patients. In conclusion, as a first step toward understanding potential links between lung mechanics and ventilation defects, impedance predictions were made using a computational airway tree model with simulated constriction of airways related to ventilation defects measured in mild‐moderate asthmatics.

Methods of airway resistance assessment.

Airway resistance is the ratio of driving pressure to the rate of the airflow in the airways. The most frequent methods used to measure airway resistance are whole-body plethysmography, the interrupter technique and the forced oscillation technique. All these methods allow to measure resistance during respiration at the level close to tidal volume, they do not require forced breathing manoeuvres or deep breathing during measurement. The most popular method for measuring airway resistance is whole-body plethysmography. The results of plethysmography include among others the following parameters: airway resistance (Raw), airway conductance (Gaw), specific airway resistance (sRaw) and specific airway conductance (sGaw). The interrupter technique is based on the assumption that at the moment of airway occlusion, air pressure in the mouth is equal to the alveolar pressure . In the forced oscillation technique (FOT), airway resistance is calculated basing on the changes in pressure and flow caused by air vibration. The methods for measurement of airway resistance that are described in the present paper seem to be a useful alternative to the most common lung function test - spirometry. The target group in which these methods may be widely used are particularly the patients who are unable to perform spirometry.

Aggravation of airway inflammation and hyper‐responsiveness following nasal challenge with Dermatophagoides pteronyssinus in perennial allergic rhinitis without symptoms of asthma

House dust mites are the most prevalent allergen causing sensitizations in patients with rhinitis and asthma in China. We aimed to investigate the changes in both upper and lower airway inflammation and responsiveness following Dermatophagoides pteronyssinus (Der-p) nasal provocation test (NPT) in rhinitis patients. Study subjects included 15 nonasthmatic Der-p-sensitized rhinitis (AR) patients with airway hyper-responsiveness (AHR) (AR+AHR+), 15 AR patients without AHR (AR+AHR-), 15 healthy controls (HCs) with Der-p sensitization (HC+DP+), and 15 HC without Der-p sensitization (HC+DP-). All subjects underwent Der-p NPT. Visual analogue scale (VAS) scores of nasal symptoms, nasal lavage and nasal airway resistance (NAR) measurement, sputum induction, and forced expiratory volume in 1 second (FEV1 ) were performed. Airway responsiveness to histamine bronchoprovocation (PD20 -FEV1 ) and exhaled nitric oxide (FeNO) was determined. NAR increased significantly in all subjects with the greatest effect seen in AR+AHR+ individuals. VAS increased in all subjects at 30 min and returned to baseline at 6 h, with significantly higher levels in AR+AHR+ and AR+AHR- subjects (P < 0.05). Eosinophils in nasal lavage fluid and sputum increased significantly after NPT in AR+AHR+ and AR+AHR- subjects (P < 0.001). FEV1 % and PD20 -FEV1 decreased and FeNO increased significantly after NPT only in AR+AHR+ subjects (P < 0.05). Nasal lavage eosinophil count was positively correlated with sputum eosinophil count and the level of FeNO and negatively correlated with FEV1 and PD20 . House dust mite nasal provocation test induces and aggravates both upper and lower airway inflammation and hyper-responsiveness in patients with persistent allergic rhinitis without asthmatic symptoms.

Alterations in DNA methylation and airway hyperreactivity in response to in utero exposure to environmental tobacco smoke

Growing evidence indicates that prenatal exposure to maternal smoking is a risk factor for the development of asthma in children. However, the effects of prenatal environmental tobacco smoke (ETS) exposure on the genome and lung immune cells are unclear. This study aims to determine whether in utero ETS exposure alters DNA methylation patterns and increases airway hyperreactivity (AHR) and inflammation. Pregnant C57BL/6 mice were exposed daily to a concentration of 1.0 mg/m3 ETS. AHR was determined in the 6-week-old offspring by measurement of airway resistance. Global and gene promoter methylation levels in lung DNA from offspring were analyzed by luminometric methylation and pyrosequencing assays, respectively. Offspring exposed to ETS showed a marked increase in the number of alveolar macrophages in the bronchoalveolar lavage fluid and level of IL-13 in the airways compared with offspring of filtered-air exposed dams (controls). ETS exposure significantly augmented AHR compared with controls. In the methylation analysis, ETS-exposed offspring had a significantly lower level of global DNA methylation than the controls. We observed a significant increase in IFN-γ, and significant decrease in IL-13 methylation levels in the ETS group compared with controls. Collectively, these data suggest that in utero ETS exposure increases the risk of pulmonary inflammation and AHR through altered DNA methylation, but additional studies are needed to fully determine the causal link between changes in methylation and cytokines levels, as well as AHR.

Lung Function Tests in Preschool Children.

The measurement of lung function by spirometry is routinely used to monitor and adequately treat children with asthma. The assessment and evaluation of lung function in children aged 3-5 years has been neglected for a long time because of the difficulty to perform forced expiratory maneuvers. However, the use of techniques such as the interrupter technique and the forced oscillation technique, which only require passive collaboration and where the only request to the child is to breathe at tidal volume, has overcome this limitation. Other techniques such as the measurement of specific airway resistance by plethysmography or the measurement of the lung clearance index using the multiple-breath washout might be helpful in this regard, although these techniques are less standardized in preschool children.

The effect of adenoidectomy on occlusal development and nasal cavity volume in children with recurrent middle ear infection

ObjectivesThe aim of the study was to examine the effect of adenoidectomy on occlusal/dentoalveolar development and nasal cavity volume in children who underwent tympanostomy tube insertion with or without adenoidectomy due to recurrent episodes of middle ear infection. MethodsThis prospective controlled study consisted of two randomly allocated treatment groups of children, younger than 2 years, who had underwent more than 3–5 events of middle ear infection during the last 6 months or 4–6 events during the last year. At the mean age of 17 months tympanostomy tube placement without adenoidectomy (Group I, n=63) tympanostomy tube placement with adenoidectomy (Group II, n=74) was performed. At the age of 5 years 41 children of the original Group I (14 females, 27 males, mean age 5.2 yrs, SD 0.17) and 59 children of the original Group II (17 females, 42 males, mean age 5.2 yrs, SD 0.18) participated in the re-examination, which included clinical orthodontic examination defining morphological and functional craniofacial status and occlusal bite index to measure upper dental arch dimensions. Acoustic rhinometry and anterior rhinomanometry was made by otorhinolaryngologist at the same day. ResultsNo statistically significant differences were found between the groups in the frequencies of morphological or functional characteristics or upper dental arch measurements or in the minimal cross-sectional areas or inspiratory nasal airway resistance measurements. ConclusionCombining adenoidectomy with tympanostomy tube insertion in the treatment of recurrent middle ear infection at an early age (under the age of 2 years) does not seem to make any difference in occlusal development in primary dentition at the age of 5 years as compared to tympanostomy tube insertion only. Since adenoid size was not evaluated, the findings do not allow interpretation that hypertrophic adenoids should not be removed in children with continuous mouth breathing or sleep disordered breathing.

Sleep onset hypoventilation in chronic spinal cord injury.

A high prevalence of sleep-disordered breathing (SDB) after spinal cord injury (SCI) has been reported in the literature; however, the underlying mechanisms are not well understood. We sought to determine the effect of the withdrawal of the wakefulness drive to breathe on the degree of hypoventilation in SCI patients and able-bodied controls. We studied 18 subjects with chronic cervical and thoracic SCI (10 cervical, 8 thoracic SCI; 11 males; age 42.4 ± 17.1 years; body mass index 26.3 ± 4.8 kg/m2) and 17 matched able-bodied subjects. Subjects underwent polysomnography, which included quantitative measurement of ventilation, timing, and upper airway resistance (RUA) on a breath-by-breath basis during transitions from wake to stage N1 sleep. Compared to able-bodied controls, SCI subjects had a significantly greater reduction in tidal volume during the transition from wake to N1 sleep (from 0.51 ± 0.21 to 0.32 ± 0.10 L vs. 0.47 ± 0.13 to 0.43 ± 0.12 L; respectively, P < 0.05). Moreover, end-tidal CO2 and end-tidal O2 were significantly altered from wake to sleep in SCI (38.9 ± 2.7 mmHg vs. 40.6 ± 3.4 mmHg; 94.1 ± 7.1 mmHg vs. 91.2 ± 8.3 mmHg; respectively, P < 0.05), but not in able-bodied controls (39.5 ± 3.2 mmHg vs. 39.9 ± 3.2 mmHg; 99.4 ± 5.4 mmHg vs. 98.9 ± 6.1 mmHg; respectively, P = ns). RUA was not significantly altered in either group. In conclusion, individuals with SCI experience hypoventilation at sleep onset, which cannot be explained by upper airway mechanics. Sleep onset hypoventilation may contribute to the development SDB in the SCI population.

Early pulmonary events of nose-only water pipe (shisha) smoking exposure in mice.

Water pipe smoking (WPS) is increasing in popularity and prevalence worldwide. Convincing data suggest that the toxicants in WPS are similar to that of cigarette smoke. However, the underlying pathophysiologic mechanisms related to the early pulmonary events of WPS exposure are not understood. Here, we evaluated the early pulmonary events of nose-only exposure to mainstream WPS generated by commercially available honey flavored “moasel” tobacco. BALB/c mice were exposed to WPS 30 min/day for 5 days. Control mice were exposed using the same protocol to atmospheric air only. We measured airway resistance using forced oscillation technique, and pulmonary inflammation was evaluated histopathologically and by biochemical analysis of bronchoalveolar lavage (BAL) fluid and lung tissue. Lung oxidative stress was evaluated biochemically by measuring the level of reactive oxygen species (ROS), lipid peroxidation (LPO), reduced glutathione (GSH), catalase, and superoxide dismutase (SOD). Mice exposed to WPS showed a significant increase in the number of neutrophils (P < 0.05) and lymphocytes (P < 0.001). Moreover, total protein (P < 0.05), lactate dehydrogenase (P < 0.005), and endothelin (P < 0.05) levels were augmented in bronchoalveolar lavage fluid. Tumor necrosis factor α (P < 0.005) and interleukin 6 (P < 0.05) concentrations were significantly increased in lung following the exposure to WPS. Both ROS (P < 0.05) and LPO (P < 0.005) in lung tissue were significantly increased, whereas the level and activity of antioxidants including GSH (P < 0.0001), catalase (P < 0.005), and SOD (P < 0.0001) were significantly decreased after WPS exposure, indicating the occurrence of oxidative stress. In contrast, airway resistance was not increased in WPS exposure. We conclude that subacute, nose-only exposure to WPS causes lung inflammation and oxidative stress without affecting pulmonary function suggesting that inflammation and oxidative stress are early markers of WPS exposure that precede airway dysfunction. Our data provide information on the initial steps involved in the respiratory effects of WPS, which constitute the underlying causal chain of reactions leading to the long-term effects of WPS.

In vivo real-time imaging of airway dynamics during bronchial challenge test.

Asthmatic patients exhibit airway hyper-responsiveness, which induces bronchoconstriction and results in a ventilation defect. The bronchial challenge test using methacholine is a useful way to measure airway hyper-responsiveness with airway constriction. Anatomical optical coherence tomography has been used to image airway hyper-responsiveness of medium sized bronchus with the aid of an endoscopic probe. Recently, a thoracic window was reported that allows direct visualization of terminal airway such as alveolus. A multi-scale integrated airway dynamics was assessed in this study. We imaged in vivo changes in the right intermedius bronchus and alveolar structure during the bronchial challenge test using two optical coherence tomography systems and correlated the changes with airway resistance. Rabbits intubated with a non-cuffed endotracheal tube on a ventilator sequentially inhaled normal saline and methacholine (2 or 5 μg/ml). The airway resistance was measured by mechanical ventilation and airway structures were monitored by a commercial endoscopic optical coherence tomography system (1,310 nm) and a house-made table-top spectral-domain optical coherence tomography system (850 nm). We demonstrated an early decrease in the size of the right intermedius bronchus and alveoli in accordance with increased airway resistance after methacholine inhalation. OCT image after inhalation of 2 μg/ml methacholine showed some segmental narrowing of the right intermedius bronchus and the image after inhalation of 5 μg/ml methacholine showed even greater segmental narrowing. The cross-sectional areas were 7.2 ± 3.3 mm2 (normal saline), 3.7 ± 2.1 mm2 (2 μg/ml methacholine), and 2.4 ± 1.1 mm2 (5 μg/ml methacholine), respectively (P = 0.04). Most of the alveolar space was collapsed under elevated airway resistance with methacholine inhalation. The averaged areas per alveolus at the end of inspiration were 0.0244 ±0.0142 mm2 (normal saline), 0.0046 ±0.0026 mm2 (2 μg/ml methacholine), and 0.0048 ±0.0028 mm2 (5 μg/ml methacholine), respectively (P = 0.03). Methacholine induced a dose-dependent increase in airway resistance (1.1 ± 0.3 cm H2O sec/ml for 2 μg/ml methacholine, 1.5 ± 0.5 cm H2O sec/ml for 5 μg/ml methacholine) (P = 0.03). These results were obtained from normal rabbits during the bronchial challenge test with a non-cuffed endotracheal tube on a ventilator. With this setup increased airway resistance possibly resulted in larger leakage around the endotracheal tube, decreased inhaled volumes, and, in turn, alveolar collapse. We performed a feasibility study of in vivo visualization of real-time airway dynamics. To our best knowledge, this is the first report of real-time integrated airway dynamics including the right intermedius bronchus and alveoli during a bronchial challenge test. OCT showed bronchial constriction and alveolar collapse with a higher methacholine dose. OCT images correlated with the measured airway resistance. Therefore, OCT could be a potential diagnostic device for airway hyper-responsiveness and airway remodeling.

Saliva-SP-D Is a Practical Marker to Identify the Peripheral Airway Inflammation

Forced oscillation technique (FOT) is a utilitarian tool to verify the localization of airway structural changes, i.e. airway remodeling by measuring airway resistance and reactance. However, the interpretation of children’s data obtained by FOT require cautions, since the airway resistance is relatively higher than that of adults and changes with age. Meanwhile, serum levels of surfactant protein D (SP-D) have been shown a biomarker of bronchial asthma.

Short-term pulmonary effects of nose-only water pipe (shisha) smoking exposure in mice

Introduction: Water pipe smoking (WPS) is a major type of smoking in Middle Eastern countries, and is increasing in popularity in Western countries. It is perceived as relatively safe; however, the underlying pathophysiological mechanisms related to the short-term pulmonary effects of WPS exposure are not understood. Objectives: The aim of this study was to investigate the short-term pulmonary effects of nose-only exposure to mainstream WPS generated by commercially available honey-flavoured tobacco. Materials and methods: BALB/c mice were exposed to WPS for 30 minutes/day for 5 days. Control mice were exposed to atmospheric air only. We measured airway resistance using forced oscillation technique, and pulmonary inflammation was evaluated histopathologically and by biochemical analysis of bronchoalveolar lavage (BAL) fluid and lung tissue. Lung oxidative stress was evaluated biochemically by measuring the level of reactive oxygen species (ROS), reduced glutathione (GSH), catalase and superoxide dismutase (SOD). Results: Mice exposed to WPS showed a significant increase in the number of neutrophils and lymphocytes. Moreover, total protein, lactate dehydrogenase and endothelin levels were augmented in BAL fluid. Tumour necrosis factor α and interleukin 6 concentrations were significantly increased in lung following exposure to WPS. ROS in lung tissue was significantly increased whereas the level and activity of antioxidants, including GSH, catalase and SOD, were significantly decreased after WPS exposure, indicating oxidative stress. By contrast, airway resistance was not increased in WPS exposure. Conclusion: Our data indicate that short-term, nose-only exposure to WPS causes lung inflammation and oxidative stress without affecting pulmonary function. These data provide information on the initial steps involved in the respiratory effects of WPS, which constitute the underlying causal chain of reactions leading to the long-term effects of WPS. Acknowledgements: Professor Abderrahim Nemmar for supervising this project.