Expiratory Flow-volume Research Articles

Closing volume and flow volume abnormalities in alpha(1)-antitrypsin phenotype groups in a community population.

Alpha1-antitrypsin phenotype groups, found in a community population studied in Tucson, were compared by using the maximum expiratory flow volume curve and the single-breath nitrogen test, alone and in combination. Subjects 25 to 54 years of age were used for the comparison, among whom there were 728 Pi M, 29 Pi MZ, and 62 Pi MS phenotypes. None of the flow volume parameters or closing volume parameters was able to differentiate among the phenotype groups; subjects in groups heterozygous for alpha1-antitrypsin did not differ from individuals homozygous for Pi M with regard to any or all flow volume or closing volume parameters.

Elite Swimmers Have Larger Lung Volumes But More Severe Bronchial Hyperresponsiveness Than Elite Cross Country Skiers

A few previous reports have shown that lung volumes, diffusion capacity as well as bronchial hyperresponsiveness (BHR) are increased in well trained swimmers as compared to other athletes and controls. It is unknown if this can be applied to elite athletes and if this is due to genetic or environmental factors such as the specificity of the swim training and the exposure to chlorine derivatives in the swimming pools. PURPOSE: To compare lung function, BHR and respiratory symptoms in elite swimmers and cross country skiers. METHODS: In a cross sectional study, 29 elite swimmers (17♂/12♀) aged 16–28 years and 30 elite cross-country skiers (20♂/10♀) aged 20–37 years, all competing at high international level, measured lung function by maximal expiratory flow volume loops, forced expiratory flow the first second (FEV1), forced vital capacity (FVC), forced expiratory flow at 50 % of FVC (FEF50) and bronchial hyperresponsiveness was measured by methacholine provocation test, provocation dose at 20 % reduction in FEV1 (PD20meth). Training time per week, symptoms and use of antiasthmatic medication were recorded with the AQUA-questionnaire and by a clinical examination. Antiasthmatic medication was withheld according to ERS guidelines. RESULTS: The elite swimmers had a significant higher FEV1, as compared to the cross country skiers, 4.73L (4.39, 5.07) mean (95 % confidence interval) vs 4.31L (4.06, 4.57) (p=0.05) respectively, FEV1 (% predicted), 114.7 % (110.2, 119.2) vs 103.0 % (99.2, 106.7) (p<0.001) respectively and FVC (% predicted), 122.4 % (116.9, 127.8) vs112.2 % (108.4, 115.9) (p=0.002) respectively. Twenty-three swimmers had a PD20meth ≤ 4 umol as compared to six cross country skiers. Mean training time per week was significant higher in swimmers, 23.8 hours (23.1, 24.4) vs 17.1 hours (16.6, 17.6) (p< 0.001). 27.6 % of the swimmers and 70 % of the skiers had an asthma diagnosis and 37.9 % of the swimmers and 83.3 % of the skiers used daily antiasthmatic medication. No differences were found in the other lung function variables or in self-reported symptoms. CONCLUSION: Elite swimmers have larger lung volumes and FEV1 than elite cross country skiers, but it seems that swimmers are more likely to develop severe BHR due to exposure to chlorine derivatives during their prolonged daily training sessions.

Aex - the area under the expiratory flow-volume loop

Preschool children often show total expiration times of less than one second in pulmonary function tests. Therefore, FEV1 cannot be used for evaluation of obstructive pulmonary diseases in small children. Aex, the area under the expiratory flow-volume loop, does not depend on the expiration time. The Aex value varies according to the convex or concave shape of the flow volume loop, can be quantified and is a valuable parameter in the diagnosis of obstructive airway diseases.In this study FEV1 und Aex values of 19882 flow-volume loops were measured and compared. The comparison shows a very high correlation coefficient of r = 0.99.The changes of both parameters in an individual after provocation or bronchospasmolysis also demonstrate a strong correlation. A 20 % change of FEV1 equals an Aex change of 36 %.We conclude that measuring Aex is a good alternative to measuring FEV1 especially if the FEV1 cannot be obtained due to short expiration times.

Classification of voluntary cough airflow patterns for prediction of abnormal spirometry.

Measurement of partial expiratory flow-volume curves has become an important technique in diagnosing lung disease, particularly in children and in the elderly. The objective of this study was to investigate the feasibility of predicting abnormal spirometry using the partial flow-volume curve generated during a voluntary cough. Here, abnormal spirometry is defined as less than the lower limit of normal (LLN) predicted by standard reference equations [1]. Cough airflow signals of 107 subjects (56 male, 51 female) were previously collected [2] from patients performing spirometry in a pulmonary function clinic. A variety of features were extracted from the airflow signal. A support vector machine (SVM) classifier was developed to predict abnormal spirometry. Airflow signal features and SVM parameters were selected using a genetic algorithm. The ability of the classifier to distinguish between normal and abnormal spirometry based on cough flow was evaluated by comparing the classifiers decisions with the LLN for the given subject's spirometry, including forced expiratory volume in one second (FEV1), forced vital capacity (FV C), and their ratio (FEV1=FV C%). Findings indicated that it was possible to classify patients whose spirometry results were less than the LLN with an overall accuracy of 76% for FEV1, 65% for FV C, and 76% for the ratio FEV1=FV C%. Accuracies were determined by repeated double cross-validation [3]. This study demonstrates the potential of using airflow measured during voluntary coughing to identify test subjects with abnormal spirometry.

Efficacy of wound analgesia for controlling post-thoracotomy pain: a randomized double-blind study†.

Continuous wound infusion of local anaesthetics has been successfully applied for postoperative pain control in several procedures but, surprisingly, it is underused in thoracic surgery. We aimed to investigate the effects of wound analgesia associated with systemic patient-controlled analgesia in patients undergoing lung cancer resection with muscle-sparing thoracotomy. Sixty consecutive patients undergoing lung cancer resection via standard muscle-sparing thoracotomy were randomized into two groups (wound analgesia and placebo groups). Bupivacaine in the wound group and free-saline solution in the placebo group were injected using a multiholed catheter connected to an elastomeric pump inserted at the end of operation between the pericostal sutures and the serratus muscle and removed 48 h after. The inter-group differences were assessed by the following criteria: (i) level of cytokines [IL-6, IL-10 and tumour necrosis factor-alpha (TNF-alpha)]; (ii) pain on a visual analogue scale at rest and after coughing; (iii) recovery of respiratory functions (flow expiratory volume in 1 s % and forced vital capacity %) and (iv) narcotic medication consumption at different time points of the postoperative course. Five out of a total of 60 patients were excluded from the final analysis. Thus, the wound and placebo groups comprised 27 and 28 patients, respectively. The wound group compared with the placebo group had a significant decrease of IL-6 (P < 0.001), IL-10 (P < 0.001) and TNF-alpha (P < 0.001) blood concentration levels, pain scores at rest (P < 0.001) and after coughing (P = 0.01), and a reduction of additional morphine intake (P = 0.03) and Ketorolac (P = 0.01) during the entire postoperative course. The recovery of the flow expiratory volume in one second % (P = 0.01) and the forced vital capacity % (P = 0.02) was also better in the wound than in the placebo group. Our data prove that wound analgesia is an effective, easy and safe procedure. It significantly reduces systemic inflammatory markers, pain scores and opioid intake; and accelerates the recovery of respiratory function. Catheter placement does not require particular manoeuvres by the surgeon nor does the elastomeric pump need any adjustment or care by physicians or nurses.

Characterization of pulmonary function in Duchenne Muscular Dystrophy.

SummaryDecline in pulmonary function in Duchenne Muscular Dystrophy (DMD) contributes to significant morbidity and reduced longevity. Spirometry is a widely used and fairly easily performed technique to assess lung function, and in particular lung volume; however, the acceptability criteria from the American Thoracic Society (ATS) may be overly restrictive and inappropriate for patients with neuromuscular disease. We examined prospective spirometry data (Forced Vital Capacity [FVC] and peak expiratory flow [PEF]) from 60 DMD patients enrolled in a natural history cohort study (median age 10.3 years, range 5–24 years). Expiratory flow‐volume curves were examined by a pulmonologist and the data were evaluated for acceptability using ATS criteria modified based on the capabilities of patients with neuromuscular disease. Data were then analyzed for change with age, ambulation status, and glucocorticoid use. At least one acceptable study was obtained in 44 subjects (73%), and 81 of the 131 studies (62%) were acceptable. The FVC and PEF showed similar relative changes in absolute values with increasing age, i.e., an increase through 10 years, relative stabilization from 10–18 years, and then a decrease at an older age. The percent predicted, FVC and PEF showed a near linear decline of approximately 5% points/year from ages 5 to 24. Surprisingly, no difference was observed in FVC or PEF by ambulation or steroid treatment. Acceptable spirometry can be performed on DMD patients over a broad range of ages. Using modified ATS criteria, curated spirometry data, excluding technically unacceptable data, may provide a more reliable means of determining change in lung function over time. Pediatr Pulmonol. 2015; 50:487–494. © 2015 Wiley Periodicals, Inc.

Reference ranges for shape indices of the flow-volume loop of healthy children.

The concavity of the descending limb of the maximum expiratory flow-volume loop (MEFVL) is the earliest change associated with airflow obstruction in small airways (ATS/ERS Task Force). The shape of the MEFVL changes with age but there are no reference values for shape indices for preschool and school children. To define pediatric reference values for spirometric data and 3 shape indices of MEFVL: 2 geometric indices: the β angle i.e., the angle between the first ½ part and the 2nd part of the MEFVL and the forced expiratory flow after 50% of the forced vital capacity (FVC) has been exhaled/peak expiratory flow (FEF50 /PEF) ratio; and a ratio that describes relative growth between airway and lung parenchyma, the forced expiratory flow between 25 and 75% of FVC/FVC ratio (FEF25-75 /FVC ratio). Data were obtained from 446 Caucasian children (2.5 to 15-year-old). The lambda, mu, sigma method was applied. References for spirometric parameters and 3 shape indices. The geometric indices decreased with age from 3 years of age (mean β angle was 215° and FEF50 /PEF ratio was 0.82) until 8 years of age (mean β angle was 191° and FEF50 /PEF ratio was 0.60) and then remained constant. The FEF25-75 /FVC ratio also decreased with age. Sex was a significant determinant for FEF25-75 /FVC ratio predicted values. This study provides standard reference equations for indices of mid-expiratory flows in children and we suggest using the FEF50 /PEF index.

Prevalence and correlates of a 'knee' pattern on the maximal expiratory flow-volume loop in young adults.

Visual inspection of the maximal flow-volume curve is an important step in interpreting spirometry. Many young people have a convex inflection or 'knee' on the expiratory part of the loop. This is thought to be a normal variant, but this view is based on theoretical grounds, and the epidemiology of the knee pattern has never been reported. Flow-volume loops from an unselected birth cohort of 1037 individuals at ages 18, 26, 32 and 38 years were visually inspected for a knee pattern. Associations with asthma diagnoses, smoking history, body mass index (BMI) and spirometry were assessed. The knee pattern was found in approximately two thirds of men and women at age 18. The prevalence decreased with age, but it was more likely to persist in women. The knee was more common after bronchodilator and was associated with higher forced expiratory volume in 1 s/forced vital capacity ratios and mid-expiratory flow rates. There was no association with smoking, except for an inverse correlation in men at age 18. No association was found with BMI. Women with asthma were less likely to have a knee at both ages 18 and 38, whereas men with asthma showed an inverse association at age 18. A knee is a very common pattern on flow-volume loop in young adults. In accordance with theoretical predictions, the prevalence of the knee declines with age, but it is more likely to persist in women. It is associated with less airflow obstruction and is less common in people with asthma.

The Influence of Body Mass Index and Weight Loss on Outcome of Elderly Patients Undergoing Lung Cancer Resection

The aim of the study was to evaluate the influence of nutritional status on outcome of elderly patients resected for lung cancer. A total of 117 consecutive patients aged ≥ 70 years undergoing lung cancer resection were enrolled. In addition to routine preoperative evaluations, other variables such as body mass index, weight loss, serum albumin, lymphocytes, and transferrin were counted. According to the body mass index value, patients were divided into Group A (≤ 18.5, underweight) and Group B (> 18.5) and risk factors for morbidity and mortality were analyzed. Group A and Group B counted 21 and 96 patients, respectively. The mean age was 74.9 ± 2.6; body mass index of Group A was significantly lower than that of Group B (16.7 ± 1.3 vs. 23.5 ± 1.7, respectively, p < 0.0001). On multivariate analysis, significant risk factors for complications were pneumonectomy (p = 0.001), stage (p = 0.006), predictive postoperative flow expiratory volume in 1 second (ppoFEV1%) (p = 0.003), and coronary disease (p = 0.04) and significant risk factors for early mortality were pneumonectomy (p = 0.0002), ppoFEV1% (p < 0.0001), BMI (0.02), and weight loss (0.007). The median survival time of Group A and Group B was 41 versus 54 months, respectively (p = 0.1). However, body mass index of less than 18.5 (p = 0.01) and weight loss of > 5% before operation (p = 0.01) were independent risk factors for 1 year mortality. In elderly patients, malnutrition was a significant additional risk factor for early death. Nutritional assessment should be included in the routine preoperative selection. In malnourished patients, nutritional support before and after operation and a careful postdischarge care might be beneficial, but it should be corroborated by further prospective studies.

A unidirectional breathing pattern improves breathing efficiency in subjects with severe COPD.

Unidirectional breathing (UB), nose-in mouth-out (NMB) or vice versa, is thought to create PEEP, stabilize small airways, and increase expiratory flow and exhaled tidal volume (VT) in patients with expiratory obstructive disorders. However, the exact mechanism providing the benefits of UB remains unknown. Our hypothesis was that the benefits of UB are achieved mainly through reduction of upper airway dead space. Sixteen stable COPD patients requiring oxygen use at home were enrolled in this prospective study at a tertiary health care center. A nasal mask and a mouthpiece were used, each having a removable one-way valve to direct the breathing pattern. Four experimentally defined patterns of spontaneous breathing, NMB, mouth-in nose-out (MNB), nose-in nose-out (NNB), and mouth-in mouth-out (MMB), were compared. Each breathing pattern lasted 5 min followed by a 5-min rest period. A NICO device continuously monitored respiratory parameters. The functional anatomical dead space volume (VD) and expired VT values were determined. Breathing efficiency (BE) was calculated as alveolar VT divided by expired volume. Functional anatomical VD was higher in bidirectional breathing (BB) (overall: 207.4 ± 7.9 mL; MMB: 232.5 ± 72.7 mL; NNB: 182.2 ± 75 mL) compared to UB (overall: 178.1 ± 87.2 mL; NMB: 176.9 ± 91.3 mL; MNB: 179.3 ± 83.2 mL) (P < .001). BE achieved with UB (overall: 76.2 ± 6.5%; NMB: 76.8 ± 6.8%; MNB: 75.6 ± 6.3%) was higher than that with BB (overall: 66.2 ± 0.09%; MMB: 64.3 ± 0.10%; NNB: 68.1 ± 0.08%) (P < .001). The difference in BE between UB and BB was more pronounced with small VT values (UB: 73.8 ± 0.08; BB: 49.4 ± 0.09) than with large VT values (UB: 77.3 ± 0.06; BB: 63.0 ± 0.07) (P < .001). Our data suggest that a reduction in functional anatomic VD may be the underlying mechanism for the benefits associated with UB in COPD patients. (ClinicalTrials.gov registration NCT00784004.).

GLCCI1 variant accelerates pulmonary function decline in patients with asthma receiving inhaled corticosteroids

In steroid-naive patients with asthma, several gene variants are associated with a short-term response to inhaled corticosteroid (ICS) treatment; this has mostly been observed in Caucasians. However, not many studies have been conducted for other ethnicities. Here, we aimed to determine the relationship between the annual decline in forced expiratory flow volume in one second (FEV1 ) and the variant of the glucocorticoid-induced transcript 1 gene (GLCCI1) in Japanese patients with asthma receiving long-term ICS treatment, taking into account the effect of high serum periostin levels, a known association factor of pulmonary function decline and a marker of refractory eosinophilic/Th2 inflammation. In this study, 224 patients with asthma receiving ICS treatment for at least 4years were enrolled. The effects of single-nucleotide polymorphisms (SNPs) in GLCCI1, stress-induced phosphoprotein 1 (STIP1), and T gene on the decline in FEV1 of 30ml/year or greater were determined. Besides the known contributing factors, that is, the most intensive treatment step, ex-smoking, and high serum periostin levels (≥95ng/ml), the GG genotype of GLCCI1 rs37973, and not other SNPs, was independently associated with a decline in FEV1 of 30ml/year or greater. When patients were stratified according to their serum periostin levels, the GG genotype of rs37973 was significantly associated with blood eosinophilia (≥250/μl) in the high serum periostin group. A GLCCI1 variant is a risk factor of pulmonary function decline in Japanese patients with asthma receiving long-term ICS treatment. Thus, GLCCI1 may be associated with response to ICS across ethnicities.

Thoracic gas compression during forced expiration in patients with emphysema, interstitial lung disease and obesity

BackgroundDynamic gas compression during forced expiration has an influence on conventional flow-volume spirometry results. The extent of gas compression in different pulmonary disorders remains obscure. Utilizing a flow plethysmograph we determined the difference between thoracic and mouth flows during forced expiration as an indication of thoracic gas compression in subjects with different pulmonary diseases characterized by limitations in pulmonary mechanics.MethodsPatients with emphysema (N = 16), interstitial lung disease (ILD) (N = 15), obesity (N = 15) and healthy controls (N = 16) were included. Compressed expiratory flow-volume curves (at mouth) and corresponding compression-free curves (thoracic) were recorded. Peak flow (PEF) and maximal flows at 75%, 50% and 25% of remaining forced vital capacity (MEF75, MEF50 and MEF25) were derived from both recordings. Their respective difference was assessed as an indicator of gas compression.ResultsIn all groups, significant differences between thoracic and mouth flows were found at MEF50 (p < 0.01). In controls, a significant difference was also measured at MEF75 (p <0.005), in emphysema subjects, at PEF and MEF75 (p < 0.05, p < 0.005) and in obese subjects at MEF75 (p <0.005) and MEF25 (p < 0.01). ILD patients showed the lowest difference between thoracic and mouth flows at MEF75 relative to controls and emphysema patients (p < 0.005, p < 0.001). Obese subjects did not differ from controls, however, the difference between thoracic and mouth flows was significantly higher than in patients with emphysema at MEF50 (p < 0.001) and MEF25 (p < 0.005).ConclusionsAlveolar gas compression distorts the forced expiratory flow volume curve in all studied groups at the middle fraction of forced expiratory flow. Consequently, mouth flows are underestimated and the reduction of flow measured at 75% and 50% of vital capacity is often considerable. However, gas compression profiles in stiff lungs, in patients with decreased elastic recoil in emphysema and in obesity differ; the difference between thoracic and mouth flows in forced expiration was minimal in ILD at the first part of forced expiration and was higher in obesity than in emphysema at the middle and last parts of forced expiration.

Computer quantification of airway collapse on forced expiration to predict the presence of emphysema

BackgroundSpirometric parameters are the mainstay for diagnosis of COPD, but cannot distinguish airway obstruction from emphysema. We aimed to develop a computer model that quantifies airway collapse on forced expiratory flow–volume loops. We then explored and validated the relationship of airway collapse with computed tomography (CT) diagnosed emphysema in two large independent cohorts.MethodsA computer model was developed in 513 Caucasian individuals with ≥15 pack-years who performed spirometry, diffusion capacity and CT scans to quantify emphysema presence. The model computed the two best fitting regression lines on the expiratory phase of the flow-volume loop and calculated the angle between them. The collapse was expressed as an Angle of collapse (AC) which was then correlated with the presence of emphysema. Findings were validated in an independent group of 340 individuals.ResultsAC in emphysema subjects (N = 251) was significantly lower (131° ± 14°) compared to AC in subjects without emphysema (N = 223), (152° ± 10°) (p < 0.0001). Multivariate regression analysis revealed AC as best indicator of visually scored emphysema (R2 = 0.505, p < 0.0001) with little significant contribution of KCO, %predicted and FEV1, %predicted to the total model (total R2 = 0.626, p < 0.0001). Similar associations were obtained when using CT-automated density scores for emphysema assessment. Receiver operating characteristic (ROC) curves pointed to 131° as the best cut-off for emphysema (95.5% positive predictive value, 97% specificity and 51% sensitivity). Validation in a second group confirmed the significant difference in mean AC between emphysema and non-emphysema subjects. When applying the 131° cut-off, a positive predictive value of 95.6%, a specificity of 96% and a sensitivity of 59% were demonstrated.ConclusionsAirway collapse on forced expiration quantified by a computer model correlates with emphysema. An AC below 131° can be considered as a specific cut-off for predicting the presence of emphysema in heavy smokers.

Characterization of the mechanical behavior of intrapulmonary percussive ventilation

A new device delivering intrapulmonary percussive ventilation (IPV), called Impulsator® (Percussionaire Corporation, Sandpoint, ID, USA), has recently been introduced in an effort to provide effective clearance and to promote homogeneity of ventilation in the lungs of patients with cystic fibrosis. In order to optimize the treatment based on its use, a better understanding of its functioning is still necessary. In fact, up to now, a complete characterization of this device has not been carried out, thus reducing its effective utilization in clinical practice. With the aim of overcoming this lack, in this study, data concerning flow and pressure delivered during in vitro IPV were acquired under different combinations of device settings and respiratory loads. Quantitative information was obtained about the physical variables administered by the device like percussive frequency, ratio of inspiratory to expiratory time, flow and pressure magnitudes and volume exchanged. The analysis of the data determined the relations among these variables and between them and the mechanical loads, laying the basis for an optimal clinical application of the device.

Airway response to exercise measured by area under the expiratory flow–volume curve in children with asthma

BackgroundThe exercise challenge test is the gold standard for diagnosing exercise-induced bronchoconstriction; however, it produces negative results in many children with postexercise symptoms. ObjectiveTo assess the utility of the area under the expiratory flow–volume curve (Aex) to identify exercise-induced bronchoconstriction in children with asthma. MethodsData from the medical records of 221 children with asthma who underwent an exercise treadmill challenge (ETC) were analyzed. The relation between exercise-induced respiratory symptoms and results of the ETC were assessed, specifically, the maximal decrease in forced expiration in 1 second (FEV1) and the maximal decrease in the Aex. ResultsThe receiver operating characteristic curve showed that a decrease greater than 6% in the Aex was an optimal cutoff point to produce the fewest misclassified ETC results based on a greater than 10% decrease in FEV1. The results of multivariable logistic regression showed that a decrease greater than 6% in the Aex was comparable to a decrease greater than 10% in FEV1 during an ETC and was more closely related to the presence of exercise-induced respiratory symptoms. Measuring the Aex during a routine ETC allowed a confirmation of bronchoconstriction in an additional 49 children (44%) with asthma and exercise-induced respiratory symptoms. The Aex measurement increased the sensitivity and negative predictive value of ETC without a significant effect on ETC specificity. ConclusionMeasuring the Aex increases the sensitivity and negative predictive value of ETC without producing a significant change in ETC specificity. Applying a 6% decrease in the Aex as a cutoff point for a positive exercise challenge test result may prevent the underdiagnosis of exercise-induced bronchoconstriction in children with asthma and postexercise symptoms. Trial RegistrationThis study was registered at www.clinicaltrials.gov (NCT01798823).

A pilot study quantifying the shape of tidal breathing waveforms using centroids in health and COPD

During resting tidal breathing the shape of the expiratory airflow waveform differs with age and respiratory disease. While most studies quantifying these changes report time or volume specific metrics, few have concentrated on waveform shape or area parameters. The aim of this study was to derive and compare the centroid co-ordinates (the geometric centre) of inspiratory and expiratory flow-time and flow-volume waveforms collected from participants with or without COPD. The study does not aim to test the diagnostic potential of these metrics as an age matched control group would be required. Twenty-four participants with COPD and thirteen healthy participants who underwent spirometry had their resting tidal breathing recorded. The flow-time data was analysed using a Monte Carlo simulation to derive the inspiratory and expiratory flow-time and flow-volume centroid for each breath. A comparison of airflow waveforms show that in COPD, the breathing rate is faster (17 ± 4 vs 14 ± 3 min(-1)) and the time to reach peak expiratory flow shorter (0.6 ± 0.2 and 1.0 ± 0.4 s). The expiratory flow-time and flow-volume centroid is left-shifted with the increasing asymmetry of the expired airflow pattern induced by airway obstruction. This study shows that the degree of skew in expiratory airflow waveforms can be quantified using centroids.

Expression and significance of Toll-like receptor-4 in rats lung established by passive smoking or associated with intratracheal instillation of lipopolysaccharide

To explore the expression and effect of Toll-like receptor 4 (TLR-4) in the lung tissue of rats established by passive smoking or intratracheal instillation of lipopolysaccharide (LPS). Eight-week-old male Sprague-Dawley rats (n = 15) were randomly divided into 3 groups, including: (1) group A: conventional breeding; (2) group B: the rats were placed into a 120-L organic glass box with twice-daily exposure to cigarette smoking plus an intratracheal instillation of water at Day 1 and 14; (3) Group C: exposure to cigarette smoking the same as group B plus intratracheal instillation of lipopolysaccharide (1 mg/kg) at Day 1 and 14. Four weeks later, general status, arterial blood gas, pulmonary function and histopathology were analyzed. The expressions of TLR-4 and nuclear factor kappa-B (NF-κB) were determined by immunohistochemistry. Western blot was used to measure the protein contents of TLR-4, NF-κB, p-Iκ-Kα/β, Iκ-Kα/β, IκB-α. And real-time polymerase chain reaction (PCR) was employed to detect the mRNA levels of tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6). Rats in Groups B and C were marantic with intermittent cough and dyspnea. Peak expiratory flow (PEF) and 50% expiratory flow-volume (EP50) were much lower in Group C ((10.6 ± 1.4), (0.77 ± 0.14) ml/s) than that in Groups A ((13.5 ± 2.0), (1.01 ± 0.08) and B (12.3 ± 0.9), (0.91 ± 0.10) ml/s) (all P < 0.05). Accumulated volume (AV) and carbon dioxide pressure (PCO2) were much higher in Groups B ((4358 ± 1501) ml, (52.77 ± 1.97) mm Hg) (1 mm Hg = 0.133 kPa) and C ((10 077 ± 1866) ml, (51.03 ± 4.96) mm Hg) than that in Group A ((1735 ± 798) ml, (39.57 ± 1.43) mm Hg) (all P < 0.05). Hematoxylin and eosin stain showed chronic bronchitis and emphysema in Groups B and C. Besides, quantitative analysis demonstrated that in unit area, mean lining interval (MLI) and destruction index (DI) in Group B ((84 ± 13) µm, 0.228 ± 0.047) and Group C ((86 ± 10) µm, 0.294 ± 0.060) significantly increased versus Group A ((65 ± 6) µm, 0.036 ± 0.012) (all P < 0.05). Immunohistochemical staining indicated that the expression of TLR-4 in cytoplasm and cytomembrane and NF-κB in nucleus markedly increased in Groups B and C versus Group A. Relative expressions of TLR-4 and NF-κB assayed by Western blot increased in Group B (0.68 ± 0.03, 0.21 ± 0.08) and Group C (1.12 ± 0.11, 0.59 ± 0.06) than that in Group A (1.36 ± 0.07, 1.04 ± 0.08). Compared with Group A, the expression levels of TLR-4, NF-κB and IκB-α and the phosphorylation levels of Iκ-Kα/β in Group B and C significantly increased (all P < 0.05). The mRNA levels of TNF-α and IL-6 increased in Group B (3.95 ± 0.29, 5.04 ± 0.28) and C (5.33 ± 0.26, 7.23 ± 0.39) versus that in Group C (1.00 ± 0.37, 1.00 ± 0.25) (all P < 0.05). Both passive smoking and intratracheal instillation of LPS may cause lung injury analogous to chronic obstructive pulmonary disease via NF-κB signaling pathway. And TLR4 plays an important role in this process.

Factors associated with aerobic fitness in adolescents with asthma

In adolescents with asthma, information on factors associated with cardiorespiratory fitness levels is limited. The present study aimed to determine if objectively measured physical activity as well as potential relevant factors such as lung function, asthma exacerbations, use of inhaled corticosteroids or skin fold thickness are associated with direct measurements of peak oxygen uptake (V˙O2peak) in adolescents with asthma. From a nested case-control study at 13-years in the Environment and Childhood Asthma birth cohort study in Oslo, Norway, 86 13-years old adolescents with and 76 without asthma performed maximal running on a treadmill with V˙O2peak measured. The sum of four skin fold thicknesses was recorded, followed by wearing an activity monitor for four consecutive days. Lung function was measured by maximum forced expiratory flow-volume curves and body plethysmography. Asthma exacerbations and use of medication were registered by parental structured interview. Data were analysed using multiple regression analysis. Vigorous physical activity (coefficients with 95% confidence intervals; 1.73 (0.32, 3.14)) and skin fold thickness -0.35 (-0.41, -0.28)) were significantly associated with V˙O2peak in adolescents with asthma. Neither use of inhaled corticosteroids, lung function nor number of asthma exacerbations was associated with V˙O2peak when taking physical activity and skin fold thickness into account. In the adolescents without asthma only skin fold thicknesses was negatively associated with V˙O2peak -3.5 (-4.1, -2.8). V˙O2peak appears to be determined by vigorous physical activity level in Norwegian adolescents with asthma and not by asthma-related factors such as use of inhaled corticosteroids, lung function nor number of asthma exacerbations.

Relationship Between Spontaneous Expiratory Flow-Volume Curve Pattern and Air-Flow Obstruction in Elderly COPD Patients

Assessment of the degree of air-flow obstruction is important for determining the treatment strategy in COPD patients. However, in some elderly COPD patients, measuring FVC is impossible because of cognitive dysfunction or severe dyspnea. In such patients a simple test of airways obstruction requiring only a short run of tidal breathing would be useful. We studied whether the spontaneous expiratory flow-volume (SEFV) curve pattern reflects the degree of air-flow obstruction in elderly COPD patients. In 34 elderly subjects (mean ± SD age 80 ± 7 y) with stable COPD (percent-of-predicted FEV(1) 39.0 ± 18.5%), and 12 age-matched healthy subjects, we measured FVC and recorded flow-volume curves during quiet breathing. We studied the SEFV curve patterns (concavity/convexity), spirometry results, breathing patterns, and demographics. The SEFV curve concavity/convexity prediction accuracy was examined by calculating the receiver operating characteristic curves, cutoff values, area under the curve, sensitivity, and specificity. Fourteen subjects with COPD had a concave SEFV curve. All the healthy subjects had convex SEFV curves. The COPD subjects who had concave SEFV curves often had very severe airway obstruction. The percent-of-predicted FEV(1)% (32.4%) was the most powerful SEFV curve concavity predictor (area under the curve 0.92, 95% CI 0.83-1.00), and had the highest sensitivity (0.93) and specificity (0.88). Concavity of the SEFV curve obtained during tidal breathing may be a useful test for determining the presence of very severe obstruction in elderly patients unable to perform a satisfactory FVC maneuver.

Expiratory muscle fatigue does not regulate operating lung volumes during high-intensity exercise in healthy humans

To determine whether expiratory muscle fatigue (EMF) is involved in regulating operating lung volumes during exercise, nine recreationally active subjects cycled at 90% of peak work rate to the limit of tolerance with prior induction of EMF (EMF-ex) and for a time equal to that achieved in EMF-ex without prior induction of EMF (ISO-ex). EMF was assessed by measuring changes in magnetically evoked gastric twitch pressure. Changes in end-expiratory and end-inspiratory lung volume (EELV and EILV) and the degree of expiratory flow limitation (EFL) were quantified using maximal expiratory flow-volume curves and inspiratory capacity maneuvers. Resistive breathing reduced gastric twitch pressure (-24 ± 14%, P = 0.004). During EMF-ex, EELV decreased from rest to the 3rd min of exercise [39 ± 8 vs. 27 ± 7% of forced vital capacity (FVC), P = 0.001] before increasing toward baseline (34 ± 8% of FVC end exercise, P = 0.073 vs. rest). EILV increased from rest to the 3rd min of exercise (54 ± 8 vs. 84 ± 9% of FVC, P = 0.006) and remained elevated to end exercise (88 ± 9% of FVC). Neither EELV (P = 0.18) nor EILV (P = 0.26) was different at any time point during EMF-ex vs. ISO-ex. Four subjects became expiratory flow limited during the final minute of EMF-ex and ISO-ex; the degree of EFL was not different between trials (37 ± 18 vs. 35 ± 16% of tidal volume, P = 0.38). At end exercise in both trials, EELV was greater in subjects without vs. subjects with EFL. These findings suggest that 1) contractile fatigue of the expiratory muscles in healthy humans does not regulate operating lung volumes during high-intensity sustained cycle exercise; and 2) factors other than "frank" EFL cause the terminal increase in EELV.