Changes In Airway Resistance Research Articles

The efficiency of polyphenolic compounds on allergen induced hyperreactivity of the airways

The results of some epidemiologic studies have suggested that the consumption of the food containing polyphenolic compounds might reduce the occurrence of asthma symptoms. The aim of our experiments was to evaluate the effect of the 21-day red-wine polyphenolic compounds (Provinol) administration on allergen (OVA) induced inflammation of the airways in experimental conditions. The allergic inflammation of the airways was induced in guinea pigs by 21-day ovalbumin sensitization. The tracheal smooth muscle reactivity was examined by in vitro method to bronchoconstricting mediator histamine (10 −8–10 −3 mol/L); the changes in airways resistance were examined by in vivo method by exposure to nebulized histamine (10 −6 mol/L). The histological investigation of the tracheal tissue and BALF levels of IL-4, IL-5 were used as parameters of the airway inflammation. A 21-day administration of Provinol caused a significant decrease of the specific airway resistance after the histamine nebulization and the decline in tracheal smooth muscle contraction amplitude to this bronchoconstrictor. Provinol minimized the degree of inflammation estimated on the basis of eosinophil calculation and levels of inflammatory cytokines IL-4 and IL5. In conclusion, the administration of Provinol leads to bronchodilating and anti-inflammatory effects in ovalbumin-sensitized guinea pigs, suggesting their possible use in the therapy of allergic inflammatory conditions of the airways.

Diesel Exhaust Particulates Exacerbate Asthma-Like Inflammation by Increasing CXC Chemokines

Particulate matter heavily pollutes the urban atmosphere, and several studies show a link between increased ambient particulate air pollution and exacerbation of pre-existing pulmonary diseases, including asthma. We investigated how diesel exhaust particulates (DEPs) aggravate asthma-like pulmonary inflammation in a mouse model of asthma induced by a house dust extract (HDE) containing cockroach allergens and endotoxin. BALB/c mice were exposed to three pulmonary challenges via hypopharyngeal administration of an HDE collected from the home of an asthmatic child. One hour before each pulmonary challenge, mice were exposed to DEP or PBS. Pulmonary inflammation was assessed by histological features, oxidative stress, respiratory physiological features, inflammatory cell recruitment, and local CXC chemokine production. To prove the role of CXC chemokines in the augmented inflammation, CXC chemokine-specific antibodies were delivered to the lungs before DEP exposure. DEP exacerbated HDE-induced airway inflammation, with increased airway mucus production, oxidative stress, inflammatory cell infiltration, bronchoalveolar lavage concentrations of CXC chemokines, and airway hyperreactivity. Neutralization of airway keratinocyte-derived chemokine and macrophage inflammatory protein-2 significantly improves the respiratory function in addition to decreasing the infiltration of neutrophils and eosinophils. Blocking the chemokines also decreased airway mucus production. These results demonstrate that DEP exacerbates airway inflammation induced by allergen through increased pulmonary expression of the CXC chemokines (keratinocyte-derived chemokine and macrophage inflammatory protein-2).

Sympathetically Mediated Changes in Capacitance

“To be accepted as a paradigm, a theory must seem better than its competitors, but it need not, and in fact never does, explain all the facts with which it can be confronted.” Thomas Kuhn, The Structure of Scientific Revolutions ### Heard on Rounds “A 57-year-old patient with a history of heart failure states that she began experiencing worsening shortness of breath 4 days prior to admission, with lower extremity edema developing 1 day prior to admission. She is compliant with her medications, though has had similar admissions previously. She states that her weight at home increased by “a couple of pounds” 2 days ago and that she increased her diuretic dose but her symptoms worsened. She says that she generally adheres to her low salt diet, but admits to eating pretzels 5 days ago. The physical examination showed BP 136/84, HR 94, weight 3 lbs above baseline, elevated JVP, basilar rales, and 1+ pedal edema.” As the intern finishes the presentation, the Senior expresses surprise that the patient's weight had increased only 3 pounds, and comments about salt and volume overload leading to acute decompensated heart failure (ADHF). The Attending adds that recent data reveal that many patients presenting with ADHF have minimal or no weight gain, but that there is no clear mechanism to explain this phenomenon. They set in place plans for diuresis, increasing vasodilators, and further patient education. On the surface, there is nothing remarkable about this case, and the usual approaches to treat this entity have remained remarkably consistent since the advent of loop diuretics over 50 years ago: salt restriction, patient education, uptitration of medications if not already at optimal doses, and diuresis. However, approximately 1 in 4 such patients are readmitted to the hospital within 30 days,1 and the disease continues to progress. It is clear …

Changes in Intramaxillary Sinus Pressure following Antrostomy, Draining Tubes, and YAMIK Procedures in 25 Patients Treated for Chronic Paranasal Sinusitis

When conservative therapies are not effective in treating sinus infections, alternate steps can be taken to improve paranasal cavity ventilation. These measures may include surgical procedures such as intranasal endoscopic or maxillary sinus fenestration, and other procedures such as placement of a maxillary sinus tube or a YAMIK sinus catheter. We conducted a prospective study of 25 patients to investigate the effects on the nasal mucosa of improved ventilation between the nasal and paranasal cavities. We accomplished this by comparing (1) the results of simultaneously measured nasal cavity and intramaxillary sinus pressures before and after widening of ventilation openings, (2) changes in mucociliary transport function as measured by the saccharin test, and (3) changes in nasal airway resistance. Just as multiple transit routes between the nasal cavity and maxillary sinus give rise to greater fluctuations in intramaxillary sinus pressure, and just as rapid breathing gives rise to even greater pressure fluctuations than does quiet breathing, we believe that both intranasal cavity airflow velocity and the number of ventilation openings present have an effect on the state of ventilation between the nasal cavity and maxillary sinus. We also suggest that the establishment of maxillary sinus ventilation openings improves mucociliary clearance.

Can exhaled inflammatory markers predict a steroid response in wheezing preschool children?

The efficacy of inhaled corticosteroids (ICS) varies among wheezing preschool children. Currently, it is not possible to predict which fraction of wheezing children will benefit from an ICS treatment. We explored whether fractional exhaled nitric oxide (FeNO) and inflammatory markers in exhaled breath condensate (EBC) can predict an ICS response in preschool wheezers. An 8-week ICS study (registered at Clinicaltrial.gov: NCT 00422747; 200 μg; beclomethasone extra-fine daily) was performed in 93 wheezing children (age range 2.0-4.4 years). At baseline, FeNO was determined off-line. EBC was collected using a closed glass-condenser. The acidity of EBC was determined and other EBC markers [interleukin (IL)-1α, IL-2, IL-4, IL-5, IL-10, soluble intercellular adhesion molecule, interferon-γ, eotaxin] were measured using a multiplex immunoassay. The change in airway resistance (Rint) and symptom score following ICS treatment was related to atopy (positive Phadiatop Infant test), FeNO and EBC markers. Airway resistance and symptoms mildly improved after ICS treatment [median (IQR): 1.4 (1.2-1.7) to 1.3 (1.1-1.5) kPa s/L, symptom score: 26 (23-28) to 28 (24-29), P < 0.01, respectively]. Only IL-10 and atopy had limited predictive value regarding a change in symptoms [β (SE) =-0.13 (0.07), P = 0.08, β (SE) = 2.05 (1.17), P = 0.08, respectively]. We did not find convincing evidence that FeNO and EBC markers could predict an ICS response in preschool wheezers. Recommendations for future studies on this topic are given.

Use of specific airway resistance to assess bronchodilator response in children

Changes in specific airway resistance (ΔsRaw) after bronchodilation, as measured by plethysmography and FEV(1) , are frequently considered to be interchangeable indices of airway obstruction. However, the baseline relationship between these two indices is weak, and the value of ΔsRaw that best predicts FEV(1) reversibility in children has yet to be determined. The aim of this study was (i) to establish the sRaw cut-off value that best distinguishes between positive and negative bronchodilator responses, as measured by FEV(1) reversibility; (ii) to determine whether the discrepancy between ΔsRaw and ΔFEV(1) might be explained by independent correlations between ΔFEV(1) and both ΔsRaw (mainly airway obstruction) and ΔFVC (airway closure); and (iii) to assess the effect of height and age on the relationship between ΔsRaw and ΔFEV(1) . A retrospective study was performed in 481 children (median age 10.5years, range 6.1-17.6) with actual or suspected asthma, for whom sRaw and spirometry data were obtained at baseline and after administration of a bronchodilator. The sRaw cut-off value that best predicted FEV(1) reversibility was a 42% decrease from baseline (P=0.0001, area under the curve 0.70, sensitivity 55%, specificity 77%) and was independent of height and age. Changes in FEV(1) were significantly but independently related to ΔsRaw and ΔFVC (index of air trapping) (r=0.40, P<0.0001 and r=0.39, P<0.0001, respectively). A 42% decrease in sRaw predicted FEV(1) reversibility reasonably well, whereas a smaller decrease in sRaw failed to detect approximately one out of two positive responses detected by FEV(1) , with no influence of height or age.

A constant‐volume ventilator and gas recapture system for hyperpolarized gas MRI of mouse and rat lungs

AbstractWe present a ventilator that enables high‐resolution proton and hyperpolarized gas MR imaging of mice and rats. The design differs from previous approaches by eliminating the need for a custom pneumatic valve located near the trachea. This permits the system to be constructed from off‐the‐shelf components and reduces dead volumes sufficiently to make HP gas MRI feasible in the mouse. The constant‐volume ventilator routinely ventilates mice and rats for period of time up to 6 hrs and maintains reproducible tidal volumes over extended image acquisition periods, as we demonstrate with high‐resolution 3D lung images in the mouse using 1H, 3He and 129Xe. The ventilator is designed to deliver a constant tidal volume regardless of changes in airway resistance, which we demonstrate with 3He MR images acquired during severe broncho‐constriction. While the images reveal clear airway narrowing, the 3He signal intensity remained within ±10% of baseline level. Finally, given the paucity of 3He and the high cost of enriched 129Xe, the ventilator has been designed to enable the recapture of these rare gases and we demonstrate a compact system to compress and store them for subsequent reprocessing. We expect that this constant‐volume ventilator will be readily reproducible by other laboratories, which we facilitate by providing extensive parts lists, detailed wiring diagrams and complete plumbing schematics. © 2011 Wiley Periodicals, Inc. Concepts Magn Reson Part B (Magn Reson Engineering) 39B: 78–88, 2011

G-CSF suppresses allergic pulmonary inflammation, downmodulating cytokine, chemokine and eosinophil production

AimsGranulocyte Colony-Stimulating Factor (G-CSF), which mobilizes hemopoietic stem cells (HSC), is believed to protect HSC graft recipients from graft-versus-host disease by enhancing Th2 cytokine secretion. Accordingly, G-CSF should aggravate Th2-dependent allergic pulmonary inflammation and the associated eosinophilia. We evaluated the effects of G-CSF in a model of allergic pulmonary inflammation. Main methodsAllergic pulmonary inflammation was induced by repeated aerosol allergen challenge in ovalbumin-sensitized C57BL/6J mice. The effects of allergen challenge and of G-CSF pretreatment were evaluated by monitoring: a) eosinophilia and cytokine/chemokine content of bronchoalveolar lavage fluid, pulmonary interstitium, and blood; b) changes in airway resistance; and c) changes in bone-marrow eosinophil production. Key findingsContrary to expectations, G-CSF pretreatment neither induced nor enhanced allergic pulmonary inflammation. Instead, G-CSF: a) suppressed accumulation of infiltrating eosinophils in bronchoalveolar, peribronchial and perivascular spaces of challenged lungs; and b) prevented ovalbumin challenge-induced rises in airway resistance. G-CSF had multiple regulatory effects on cytokine and chemokine production: in bronchoalveolar lavage fluid, levels of IL-1 and IL-12 (p40), eotaxin and MIP-1a were decreased; in plasma, KC, a neutrophil chemoattractant, was increased, while IL-5 was decreased and eotaxin was unaffected. In bone-marrow, G-CSF: a) prevented the increase in bone-marrow eosinophil production induced by ovalbumin challenge of sensitized mice; and b) selectively stimulated neutrophil colony formation. SignificanceThese observations challenge the view that G-CSF deviates cytokine production towards a Th2 profile in vivo, and suggest that this neutrophil-selective hemopoietin affects eosinophilic inflammation by a combination of effects on lung cytokine production and bone-marrow hemopoiesis.

Determining When Enhanced Pause (Penh) is Sensitive to Changes in Specific Airway Resistance

Penh is a dimensionless index normally used to evaluate changes in the shape of the airflow pattern entering and leaving a whole-body flow plethysmograph as an animal breathes. The index is sensitive to changes in the distribution of area under the waveform during exhalation and increases in a nonlinear fashion as the normalized area increases near the beginning of the curve. Enhanced pause (Penh) has been used to evaluate changes in pulmonary function and as a method to evaluate airway reactivity. However, the use of Penh to assess pulmonary function has been challenged (Bates et al., 2004; Lundblad et al., 2002; Mitzner et al., 2003; Mitzner & Tankersley, 1998; Petak et al., 2001; Sly et al., 2005). The objective of this study was to show how Penh of the thorax and plethysmograph flow patterns are related. That relationship is used to describe the conditions under which whole-body plethysmograph Penh measurements can be used to detect changes in sRaw.

Adverse events associated with treatment of latent tuberculosis in the general population

Guidelines recommend treatment of latent tuberculosis in patients at increased risk for active tuberculosis. Studies investigating the association of therapy with serious adverse events have not included the entire treated population nor accounted for comorbidities or occurrence of similar events in the untreated general population. Our objective was to estimate the risk of adverse events requiring hospital admission that were associated with therapy for latent tuberculosis infection in the general population. Using administrative health data from the province of Quebec, we created a historical cohort of all residents dispensed therapy for latent tuberculosis between 1998 and 2003. Each patient was matched on age, sex and postal region with two untreated residents. The observation period was 18 months (from 6 months before to 12 months after initiation of therapy). The primary outcome was hospital admission for therapy-associated adverse events. During the period of observation, therapy for latent tuberculosis was dispensed to 9145 residents, of whom 95% started isoniazid and 5% started rifampin. Pretreatment comorbid illness was significantly more common among patients receiving such therapy compared with the matched untreated cohort. Of all patients dispensed therapy, 45 (0.5%) were admitted to hospital for a hepatic event compared with 15 (0.1%) of the untreated patients. For people over age 65 years, the odds of hospital admission for a hepatic event among patients treated for latent tuberculosis infection was significantly greater than among matched untreated people after adjustment for comorbidities (odds ratio [OR] 6.4, 95% CI 2.2-18.3). Excluding patients with comorbid illness, there were two excess admissions to hospital for hepatic events per 100 patients initiating therapy compared with the rate among untreated people over 65 years (95% CI 0.1-3.87). The risk of adverse events requiring hospital admission increased significantly among patients over 65 years receiving treatment for latent tuberculosis infection. The decision to treat latent tuberculosis infection in elderly patients should be made after careful consideration of risks and benefits.

Response of nasal airway and heart rate variability to controlled nasal breathing

To investigate the responses of nasal airway and autonomic nervous system (ANS) under controlled nasal breathings. Ten healthy volunteers, aged between 21 and 37 years, were enrolled. The participants breathed either through bilateral nostrils (BNB) or unilaterally through the left nostril (UNB) at 0.25 Hz for 5 min. The electrocardiography was simultaneously recorded and the ANS activities were evaluated using heart rate variability analysis. Nasal airway resistance and related factors were measured by rhinomanometry. The results showed that the mean heartbeat interval during UNB was significantly greater than during BNB. The sympathetic modulation decreased significantly during UNB. The correlations between nasal airway resistance and mean heartbeat interval were significant for both UNB and BNB. The increase of heartbeat intervals during UNB was associated with the decrease of cardiac sympathetic activities. The changes of ANS activities and nasal airway resistance during UNB are similar to the changes caused by a prolonged lying.

Anatomical and functional changes in the upper airways of sleep apnea patients due to mandibular repositioning: A large scale study

The obstructive sleep apnea-hypopnea syndrome (OSAHS) is a sleep related breathing disorder. A popular treatment is the use of a mandibular repositioning appliance (MRA) which advances the mandibula during the sleep and decreases the collapsibility of the upper airway. The success rate of such a device is, however, limited and very variable within a population of patients. Previous studies using computational fluid dynamics have shown that there is a decrease in upper airway resistance in patients who improve clinically due to an MRA. In this article, correlations between patient-specific anatomical and functional parameters are studied to examine how MRA induced biomechanical changes will have an impact on the upper airway resistance. Low-dose computed tomography (CT) scans are made from 143 patients suffering from OSAHS. A baseline scan and a scan after mandibular repositioning (MR) are performed in order to study variations in parameters. It is found that MR using a simulation bite is able to induce resistance changes by changing the pharyngeal lumen. The change in minimal cross-sectional area is the best parameter to predict the change in upper airway resistance. Looking at baseline values, the ideal patients for MR induced resistance decrease seem to be women with short airways, high initial resistance and no baseline occlusion.

The efficiency of polyphenolic compounds on allergen induced hyperreactivity of the airways

The results of some epidemiologic studies have suggested that the consumption of the food containing polyphenolic compounds might reduce the occurrence of asthma symptoms. The aim of our experiments was to evaluate the effect of the 21-day red-wine polyphenolic compounds (Provinol) administration on allergen (OVA) induced inflammation of the airways in experimental conditions. The allergic inflammation of the airways was induced in guinea pigs by 21-day ovalbumin sensitization. The tracheal smooth muscle reactivity was examined by in vitro method to bronchoconstricting mediator histamine (10 −8–10 −3 mol/L); the changes in airways resistance were examined by in vivo method by exposure to nebulized histamine (10 −6 mol/L). The histological investigation of the tracheal tissue and BALF levels of IL-4, IL-5 were used as parameters of the airway inflammation. A 21-day administration of Provinol caused a significant decrease of the specific airway resistance after the histamine nebulization and the decline in tracheal smooth muscle contraction amplitude to this bronchoconstrictor. Provinol minimized the degree of inflammation estimated on the basis of eosinophil calculation and levels of inflammatory cytokines IL-4 and IL5. In conclusion, the administration of Provinol leads to bronchodilating and anti-inflammatory effects in ovalbumin-sensitized guinea pigs, suggesting their possible use in the therapy of allergic inflammatory conditions of the airways.

Protective effect of limb ischemic preconditioning on acute lung injury induced by lipopolysaccharide in rats

To explore the protective effect of noninvasive limb ischemic preconditioning (N-LIP) on acute lung injury (ALT) induced by lipopolysaccharide (LPS) in rats. Fifteen female SD rats were randomly divided into a control group, an acute lung injury group (ALI group), an acute lung injury and noninvasive limb ischemic preconditioning group (ALI+N-LIP group). After ALI rats were treated with N-LIP, the changes of airway resistance (AR) and dynamic compliance (Cdyn) were tested by invasive pulmonary function system and recorded. Blood samples and bronchoalveolar lavage fluid (BALF) were collected, the amounts of white blood cell (WBC) in BALF were counted by cytometry, and the level of lactate dehydrogenase (LDH) in BALF was also examined by automatic biochemistry analyzer. The level of serum superoxide dismutase (SOD) and malondialdehyd (MDA) was examined by chromatometry. The lung tissues were acquired to observe the expression of pulmonary surfactant-associated protein-A (SP-A) and pathological changes. After being stimulated by methacholine (Mch), the increasing rate of AR and decreasing rate of Cdyn in the ALI+N-LIP group were less than those in the ALI group (P<0.01). The levels of WBC and LDH in BALF in the ALI+N-LIP group were much lower than those in the ALI group (P<0.05). Meanwhile, the activity of serum SOD in the ALI+N-LIP group was higher, and the level of serum MDA was lower than that in the ALI group (P<0.05). The expression of SP-A in the lung tissue in the ALI+N-LIP group was the highest in the 3 groups, while that in the ALI group was the weakest (P<0.01). Injury of the lung tissue in the ALI+N-LIP group was less than that in the ALI group, but more severe than that in the control group. N-LIP has protective effect on acute lung injury induced by LPS in rats. The possible mechanism is related to improving the secretion of SP-A and antioxidation.

Rebuttal from Sheel and McKenzie

POINT:COUNTERPOINTPulmonary edema does/does not occur in human athletes performing heavy sea-level exerciseRebuttal from Sheel and McKenziePublished Online:01 Oct 2010https://doi.org/10.1152/japplphysiol.01353.2009cMoreSectionsPDF (41 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Within the Point presented by Dr. Hopkins (2) several case studies, which have little to do with the debate, are presented as “evidence” of the development of pulmonary edema during heavy sea-level exercise. Anecdotal reports of pulmonary edema induced by emotional stress, sexual intercourse, and exercise at high altitude are all distractions from the central question. Moreover, left ventricular diastolic dysfunction is likely causative in these instances (8) and they represent an entirely different physiological scenario than that of the healthy athlete performing near-maximal exercise at sea level.We disagree with the assertion that the rapid infusion of 20 ml/kg of normal saline into resting humans can be used as supporting evidence for exercise-induced interstitial edema (4). Rather, it produces a nonphysiological situation (i.e., volume overload by ∼1.5 liters), which results in airflow obstruction and changes to airway responsiveness that are not commensurate with the typical exercise response seen in the population being discussed in this debate.Our colleague (2) and others (5) argue that the persistence of V̇A/Q̇ inequality during recovery from heavy exercise supports the idea of an exercise-induced increase in extravascular lung water. Specifically, the logic is that interstitial edema compresses the small airways and blood vessels resulting in a mismatch of V̇A/Q̇. However, this is not direct evidence of edema and should not be interpreted as such. As clearly stated within the concluding statements of the original manuscript by Schaffartzik et al. (5): “It [persistent V̇A/Q̇ mismatch owing to pulmonary interstitial edema] is of course not proof of the hypothesis.” We agree. Alternative explanations for V̇A/Q̇ heterogeneity include changes in airway resistance and increases in dead-space ventilation (6, 7). Moreover, increased V̇A/Q̇ heterogeneity with sustained heavy exercise does not result in a change in MRI-derived lung density measures 20 min following exercise (1). The multiple inert-gas elimination technique for determining V̇A/Q̇ has never been directly validated (3) which makes definitive statements about the development of exercise-induced edema difficult. Furthermore, regional estimates of where the edema (i.e., peribronchial and perivascular “cuffing”) occurs based on V̇A/Q̇ heterogeneity measures in humans are speculative. It appears that the indirect methods offer only cause for speculation on the presence of pulmonary edema while direct measurements via CT or MRI consistently fail to demonstrate changes in lung density.Accumulation of scattered anecdotal reports and circumstantial evidence is not proof of interstitial edema. In our view, the hypothesis continues to await experimental support.REFERENCES1. Burnham KJ , Arai TJ , Dubowitz DJ , Henderson AC , Holverda S , Buxton RB , Prisk GK , Hopkins SR. Pulmonary perfusion heterogeneity is increased by sustained, heavy exercise in humans. J Appl Physiol 107: 1559–1568, 2009.Link | ISI | Google Scholar2. Hopkins SR. Counterpoint: Pulmonary edema does occur in human athletes performing heavy sea-level exercise. J Appl Physiol; doi:10.1152/japplphysiol.01353-2009.Google Scholar3. Hopkins SR , Levin DL , Emami K , Kadlecek S , Yu J , Ishii M , Rizi RR. Advances in magnetic resonance imaging of lung physiology. J Appl Physiol 102: 1244–1254, 2007.Link | ISI | Google Scholar4. Prisk GK , Olfert IM , Arai TJ , Wagner PD , Hopkins SR. Rapid intravenous infusion of 20 ml/kg saline does not impair resting pulmonary gas exchange in the healthy human lung. J Appl Physiol 108: 53–59, 2010.Link | ISI | Google Scholar5. Schaffartzik W , Poole DC , Derion T , Tsukimoto K , Hogan MC , Arcos JP , Bebout DE , Wagner PD. VA/Q distribution during heavy exercise and recovery in humans: implications for pulmonary edema. J Appl Physiol 72: 1657–1667, 1992.Link | ISI | Google Scholar6. Tsukimoto K , Arcos JP , Schaffartzik W , Wagner PD , West JB. Effect of common dead space on VA/Q distribution in the dog. J Appl Physiol 68: 2488–2493, 1990.Link | ISI | Google Scholar7. Wagner PD , Gale GE , Moon RE , Torre-Bueno JR , Stolp BW , Saltzman HA. Pulmonary gas exchange in humans exercising at sea level and simulated altitude. J Appl Physiol 61: 260–270, 1986.Link | ISI | Google Scholar8. Wilmshurst PT. Pulmonary oedema induced by emotional stress, by sexual intercourse, and by exertion in a cold environment in people without evidence of heart disease. Heart (Br Cardiac Soc) 90: 806–807, 2004.Crossref | ISI | Google Scholar Download PDF Previous Back to Top Next FiguresReferencesRelatedInformation More from this issue > Volume 109Issue 4October 2010Pages 1274-1275 Copyright & PermissionsCopyright © 2010 the American Physiological Societyhttps://doi.org/10.1152/japplphysiol.01353.2009cPubMed20940440History Published online 1 October 2010 Published in print 1 October 2010 Metrics

IL-1β acutely increases pulmonary SP and permeability without associated changes in airway resistance and ventilation in anesthetized rats

Bronchopulmonary C-fibers (PCFs), when activated, promote substance P (SP) release, increase microvascular leak, and produce bronchoconstriction and apnea. IL-1β administered systemically or locally into the pulmonary parenchyma stimulates PCFs. Thus, we tested whether right atrial bolus injection or aerosol inhalation of IL-1β, to mainly stimulate PCFs, would acutely affect pulmonary SP level and vascular permeability, airway resistance (R(L)), and ventilation in anesthetized rats. Our results showed that 30min after IL-1β injection (2-6 μg kg⁻¹), SP levels and Evans blue extravasation in bronchoalveolar lavage fluid were markedly increased and these responses were eliminated or largely reduced in neonatal capsaicin-treated rats. In contrast, neither injection nor inhalation of IL-1β (5-15 μg ml⁻¹) significantly altered R(L) and ventilation. Additionally, the capsaicin-evoked (4 μg kg⁻¹, i.v.) apneic response was unaffected by IL-1β treatment. Our data suggest that IL-1β, as administered in this study, can acutely increase pulmonary SP and vascular permeability, likely via stimulating PCFs, with little impact on R(L) and ventilation.

Sono e doenças pulmonares crônicas: pneumopatias intersticiais difusas, asma brônquica e DPOC

Chronic lung diseases can be aggravated by various factors and comorbidities, including sleep-disordered breathing. Although changes in the quality of life of patients with chronic lung disease are usually related to daytime variables, the physiological changes in sleep impair the quality of sleep and interfere with the natural history of the disease. Alterations in sleep architecture appear to be a common mechanism in these diseases. During sleep, the upper and lower airways are more interconnected: changes in upper airway resistance during sleep are added to the severe resistive alterations in the lower airways due to asthma and COPD. In addition, there are complex mechanical and ventilatory interactions. The recognition of these interactions allows better assessment of the exacerbations and the progression of chronic lung diseases.

Pharmacological validation of a telemetric model for the measurement of bronchoconstriction in conscious rats

Introduction: Telemetric measurement of intra-pleural pressure in conscious animals that are restrained in head-out plethysmography chambers enables determination of airway resistance. Originally proposed over 10 years ago, pharmacological validation of this technique is limited. Here airway resistance in conscious, instrumented rats was compared to measurement in anaesthetised rats via a fluid filled oesophageal catheter following administration of two different pharmacological agents. Methods: Male rats were implanted with telemetry devices and were trained to accept the restraint of head-out plethysmography chambers. A separate group of male rats were anaesthetised, placed in a body-enclosed plethysmography chamber and were prepared with a tracheal, oesphageal and jugular vein cannulae. Methacholine or NECA were given intravenously and changes in ventilation and airway resistance were measured. Results: The pressure signal obtained in the telemetered rats was found to be extremely variable. Variability was confounded by excessive struggling, particularly during the infusion periods. Misplacement of the pressure sensitive catheter tip and prior habituation to the chamber were not factors in signal variability. Consequently, no dose–response relationship to either pharmacological agent was established in this model. Dose-dependent increases in resistance to both methacholine and NECA were measured in anaesthetised rats using body-enclosed plethysmography. Discussion: Given the variability of the pressure signal within and between rats, the feasibility of a model in conscious rats for the measurement of airway resistance is questioned. Improved restraint methods or alternative models in conscious animals should therefore be explored. In the meantime, assessment of airway resistance is best confined to the anaesthetised rat.

Intratracheal Sensitization/Challenge-Induced Biphasic Asthmatic Response and Airway Hyperresponsiveness in Guinea Pigs

In most experimental model of asthma using guinea pigs, the animals are made to inhale an aerosolized antigen which passes through the nasal cavity. In the present study, we attempted to create an animal model of asthma showing a biphasic asthmatic response and airway hyperresponsiveness, in which the allergic responses are restricted to the lung. Guinea pigs were sensitized by the intratracheal instillation of ovalbumin (OVA)+Al(OH)₃ once a day for 7 d, and then intratracheally challenged with OVA 12 d after the last sensitization. The change in specific airway resistance (sRaw) and airway responsiveness to histamine were measured. Pranlukast (100 mg/kg), theophylline (50 mg/kg), and dexamethasone (10 mg/kg) were orally administered 18 and 2 h before the antigen challenge. The challenge caused a marked biphasic elevation of sRaw with peaks at 5 min and 4 h. At 24 h, airway hyperresponsiveness to histamine was observed. Pranlukast, theophylline, and dexamethasone suppressed the late asthmatic response and airway hyperresponsiveness. The early asthmatic response was inhibited by theophylline and dexamethasone. In conclusion, the intratracheal sensitization and challenge caused a biphasic asthmatic response and airway hyperresponsiveness in guinea pigs. This model may be useful for the evaluation of anti-asthma drugs.

Effects of Flavin7 on allergen induced hyperreactivity of airways

Some studies have suggested that the polyphenolic compounds might reduce the occurrence of asthma symptoms. The aim of our experiments was to evaluate the effects of 21 days of the flavonoid Flavin7 administration on experimentally induced airway inflammation in ovalbumin-sensitized guinea pigs. We assessed tracheal smooth muscle reactivity by an in vitro muscle-strip method; changes in airway resistance by an in vivo plethysmographic method; histological picture of tracheal tissue; and the levels of interleukin 4 (IL-4), and interleukin 5 (IL-5) in bronchoalveolar lavage fluid (BALF). Histological investigation of tracheal tissue and the concentrations of the inflammatory cytokines IL-4 and IL-5 in BALF were used as indices of airway inflammation. Administration of Flavin7 caused a significant decrease of specific airway resistance after histamine nebulization and a decline in tracheal smooth muscle contraction amplitude in response to bronchoconstricting mediators. Flavin7 minimized the degree of inflammation estimated on the basis of eosinophil calculation and IL-4 and IL-5 concentrations. In conclusion, administration of Flavin7 showed bronchodilating and anti-inflammatory effects on allergen-induced airway inflammation.