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Masafumi Yamamoto,1 Satoshi Konno,2 Hironi Makita,2,3 Katsuaki Nitta,4 Kaoruko Shimizu,2 Masaru Suzuki,2 Mutsumi Nishida,1 Junichi Sugita,1 Takanori Teshima,1 Masaharu Nishimura2,3 1Division of Laboratory and Transfusion Medicine, Hokkaido University Hospital, Sapporo, Hokkaido, Japan; 2Department of Respiratory Medicine, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan; 3Hokkaido Institute of Respiratory Diseases, Sapporo, Hokkaido, Japan; 4Makita Hospital, Sapporo, Hokkaido, JapanCorrespondence: Masaharu NishimuraDepartment of Respiratory Medicine, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, N-15 W-7, Kita-Ku, Sapporo, 060-8638, JapanTel +81-11-706-5911Fax +81-11-706-7899Email ma-nishi@med.hokudai.ac.jpBackground: Generally, the maximal expiratory flow–volume (MEFV) curve must be measured for the diagnosis and staging of chronic obstructive pulmonary disease (COPD). As this test is effort dependent, international guidelines recommend that three acceptable trials are required for each test. However, no study has examined the magnitude and factors for the variability in parameters among three acceptable trials.Methods: We evaluated the intra-individual variations in several parameters among three acceptable MEFV curves obtained at one-time point in patients with COPD (n = 28, stage 1; n = 36, stage 2; n = 21, stages 3– 4). Next, the factors for such variations were examined using forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC).Results: The averages of coefficient of variation (CV) for FEV1 and FVC were 2.0% (range: 1.0– 3.0%) and 1.6% (0.9– 2.2%), respectively. Both parameters were significantly better than peak expiratory flow rate, forced expiratory flow at 50% of expired FVC, and forced expiratory flow at 75% of expired FVC (CVs: 5.0– 6.9%). A higher spirometric stage was significantly associated with higher CVs for FVC and FEV1, and older age was significantly correlated with a higher variation in FEV1 alone. Furthermore, a significantly inverse association was observed between emphysema severity, and the CVs for FEV1, but not that for FVC, regardless of spirometric stage.Conclusion: Both FVC and FEV1 are highly reproducible; nevertheless, older age, lower FEV1 at baseline, and non-emphysema phenotype are factors for a higher variability in FEV1 in patients with COPD.Keywords: chronic obstructive pulmonary disease, coefficient of variation, flow–volume curve, forced expiratory volume in 1 second, variability

Bronchial collapse due to bronchomalacia is an important cause of chronic coughing in dogs. Radiographic and CT evidence of bronchial collapse has previously been reported in healthy Beagle dogs under forced expiration. However, published studies in brachycephalic dog breeds that are prone to bronchial collapse are currently lacking. In the present prospective analytical experimental study, CT and radiography were used to measure the bronchial diameter and collapsibility of each pulmonary bronchus during end-expiratory, 5 mL/kg forced-expiratory, and 10 mL/kg forced-expiratory phases in 17 asymptomatic brachycephalic dogs and six healthy Beagle dogs. Bronchial collapsibility was significantly greater during forced expiration, than that at the end of expiration in both groups (P < .001). Bronchial collapsibility measurements of the left lung lobes and the right cranial, middle, and accessory lobes were significantly higher in asymptomatic brachycephalic dogs than those in healthy Beagle dogs, during all expiratory phases (P < .05). The higher bronchial collapsibility of brachycephalic dogs was also supported using CT multiplanar reconstruction images and radiography. In conclusion, radiographic and CT measures of bronchial collapsibility in asymptomatic brachycephalic dogs are higher than measures in healthy Beagle dogs. Therefore, measures of bronchial collapse in brachycephalic dogs should not be evaluated using the same baseline measures as those used for healthy Beagle dogs.

Adult survivors of very preterm (≤32 wk gestational age) birth without (PRE) and with bronchopulmonary dysplasia (BPD) have variable degrees of airflow obstruction at rest. Assessment of the shape of the maximal expiratory flow-volume (MEFV) curve in PRE and BPD may provide information concerning their unique pattern of airflow obstruction. The purposes of the present study were to 1) quantitatively assess the shape of the MEFV curve in PRE, BPD, and healthy adults born at full-term (CON), 2) identify where along the MEFV curve differences in shape existed between groups, and 3) determine the association between an index of MEFV curve shape and characteristics of preterm birth (i.e., gestational age, mass at birth, duration of oxygen therapy) in PRE and BPD. To do so, we calculated the average slope ratio (SR) throughout the effort-independent portion of the MEFV curve and at increments of 5% of forced vital capacity (FVC) between 20 and 80% of FVC in PRE ( n = 19), BPD ( n = 25), and CON ( n = 20). We found that average SR was significantly higher in PRE (1.34 ± 0.35) and BPD (1.33 ± 0.45) compared with CON (1.03 ± 0.22; both P < 0.05) but similar between PRE and BPD ( P = 0.99). Differences in SR between groups occurred early in expiration (i.e., 20–30% of FVC). There was no association between SR and characteristics of preterm birth in PRE and BPD groups (all P > 0.05). The mechanism(s) of increased SR during early expiration in PRE/BPD relative to CON is unknown but may be due to differences in the structural and mechanical properties of the airways.

A concave-shaped maximal expiratory flow-volume (MEFV) curve is a spirometric feature in chronic obstructive pulmonary disease (COPD). The MEFV curve is characterized by an increase in the Obstructive Index, which is defined as a ratio of forced vital capacity to the volume-difference between two points of half of the peak expiratory flow on the MEFV curve. We hypothesized that the Obstructive Index would reflect the severity of emphysema in patients with COPD and asthma-COPD overlap (ACO). Thus, the aim of this retrospective study was to evaluate whether the Obstructive Index on spirometry is associated with the extent of emphysema on computed tomography (CT) in patients with COPD, ACO, and asthma (N = 65, 15, and 53, respectively). The percentage of low-attenuation volume (LAV%) and wall area (WA%) were measured on CT. The Obstructive Index was higher in patients with COPD and ACO than in those with asthma. Spearman correlation showed that a greater Obstructive Index was associated with a higher LAV%, but not WA%. Multivariate analysis showed that Obstructive Index was associated with LAV% (standardized β = 0.43, P

Patients who have chronic obstructive pulmonary disease (COPD) and bronchial asthma (BA) share symptoms such as, dyspnoea, cough and wheeze. Differentiating these diseases in the ambulatory setting can be challenging especially in older adult smokers who are being treated with a variety of medications. The objective of this study was to test the value of adding a maximal inspiratory manoeuvre to basic spirometry to differentiate COPD and BA. One hundred forty-three COPD patients and 142 BA patients had measurements of maximal inspiratory and expiratory flow during routine spirometry. Parameters from these tests were used to assess diagnostic accuracy using receiver-operating characteristic (ROC) analyses followed by logistic regression. The association of two independent parameters were analyzed using linear regression analyses. Results show that forced expiratory volume in one second/forced vital capacity (FEV

Intrapleural pressure during a forced vital capacity (VC) maneuver is often in excess of that required to generate maximal expiratory airflow. This excess pressure compresses alveolar gas (i.e., thoracic gas compression [TGC]), resulting in underestimated forced expiratory flows (FEFs) at a given lung volume. It is unknown if TGC is influenced by sex; however, because men have larger lungs and stronger respiratory muscles, we hypothesized that men would have greater TGC. We examined TGC across the “effort‐dependent” region of VC in healthy young men (n = 11) and women (n = 12). Subjects performed VC maneuvers at varying efforts while airflow, volume, and esophageal pressure (POES) were measured. Quasistatic expiratory deflation curves were used to obtain lung recoil (PLUNG) and alveolar pressures (i.e., PALV = POES–PLUNG). The raw maximal expiratory flow–volume (MEFVraw) curve was obtained from the “maximum effort” VC maneuver. The TGC‐corrected curve was obtained by constructing a “maximal perimeter” curve from all VC efforts (MEFVcorr). TGC was examined via differences between curves in FEFs (∆FEF), area under the expiratory curves (∆AEX), and estimated compressed gas volume (∆VGC) across the VC range. Men displayed greater total ∆AEX (5.4 ± 2.0 vs. 2.0 ± 1.5 L2·s−1; p, We sought to examine whether sex influences the degree to which thoracic gas compression (TGC) underestimates forced expiratory flows at a given lung volume during forced expiration. Men displayed greater TGC than women, particularly at 25% of the forced expired volume. This greater TGC was likely due to greater expiratory pressures generated by men throughout the maneuver. Failure to appropriately account for TGC results in a greater underestimation of expiratory airflow in men, primarily during the early phase of forced expiration.

Background Crohn’s disease (CD) and Familial Mediterranean fever (FMF) are both inflammatory disorders characterised by recurrent abdominal pain and fever attacks. Mutations of Mediterranean (MEFV) gene appear to be associated with stricturing behaviour and extraintestinal manifestations of CD. Further clinical studies regarding progression of CD in coexistence with FMF is still required. The aim of this study was to evaluate the influence of concomitant FMF in CD patients on the course of the CD in FMF endemic area. Methods Total 210 adult patients who had diagnosed with CD with or without FMF between November 2006 and April 2019 were respectively examined. FMF diagnoses were based on Tel-Hashomer criteria. The Montreal classification was used to define location and behaviour of CD. CD patients were divided into two groups FMF positive and FMF negative. Severity of CD was assessed by the need for hospitalisation related to CD, whether biological therapy was received and/or whether surgery was undergone due to CD. All demographic features, MEFV mutations, location/behaviour of disease, and extraintestinal manifestations were analysed retrospectively. Results In the present study, 8 (3.8%) of the total 210 CD patients have concomitant FMF. Mean follow-up time in CD-FMF was 59.55 months and CD-non-FMF was 60.98 months. CD patients with or without FMF showed similar demographic features including age, sex, smoking behaviour, disease location, behaviour, and treatment regimen in maintenance of the remission. Regarding extraintestinal manifestations, only peripheral arthritis was found significantly higher in CD-FMF patients (n = 3, 37.5%) compared CD-non-FMF patients (n = 21, 10.4%). In the CD-FMF patients, a result of MEFV mutation gene analysis was found in medical records 6 patients. Of those, 2 had homozygote MEFV mutation, 2 had heterozygote MEFV mutation and 2 without any MEFV mutations. In CD-FMF group, percentage of patients on biological therapy (n = 4, 50%) was significantly higher than CD-non FMF group (n = 24, 11.9%) (p = 0.012). Steroid dependence and hospitalisation in CD-FMF (n = 3, 37.5% and n = 5, 62.5%) group were relatively higher than CD-non-FMF (n = 83, 41.1%) group, but not statistically significant. The percentage of CD-FMF patients who underwent intestinal surgery (n = 1, 12.5%) was similar to that of CD-non-FMF (n = 33, 16.3%). Conclusion In the current study, the prevalence of FMF in CD patients was detected 3.8% in FMF endemic area. The group of patients on biological therapy in CD-FMF patients was significantly higher than CD-non-FMF patients. Frequency of hospitalisation in CD-FMF patients was relatively higher than CD-non-FMF patients. Our findings indicate that concomitant FMF in CD patients may have a negative effect on the course of CD.

BACKGROUND: Lung function parameters are used as signs in the diagnosis and evaluation of asthma; however, their sensitivity and specificity are not ideal. We calculated and combined angle β with lung function parameters to identify the ideal indicator. OBJECTIVE: We aimed to identify an ideal indicator for evaluating the severity of airway obstruction in children with asthma. METHODS: In total, 151 school-age children diagnosed with asthma were selected as the asthma group, and 106 healthy children were selected as the control group. The subjects were divided into the exacerbation group, chronic persistent group, and clinical remission group. Furthermore, the subjects were classified into mild and moderate groups or severe and critical groups. Angle β was calculated in each group. A receiver operating characteristic curve analysis was performed to determine the cutoff values of angle β and lung function parameters that together provided high sensitivity and specificity for airway obstruction evaluation in children with asthma. RESULTS: The mean value of angle β in the asthma group was significantly smaller than that in the control group (178.18° and 196.72°, respectively, P CONCLUSIONS: Angle β was a useful indicator for assessing airway obstruction. Furthermore, angle β combined with FEV1, FEV1/FVC%, FEF25%, FEF50%, and FEF75% can enhance the sensitivity and specificity of airway obstruction evaluations.

Background The expiratory time constant (RCEXP), which is defined as the product of airway resistance and lung compliance, enable us to assess the mechanical properties of the respiratory system in mechanically ventilated patients. Although RCEXP could also be applied to spontaneously breathing patients, little is known about RCEXP calculated from the maximal expiratory flow-volume (MEFV) curve. The aim of our study was to determine the reference value for RCEXP, as well as to investigate the association between RCEXP and other respiratory function parameters, including the forced expiratory volume in 1 s (FEV1)/ forced vital capacity (FVC) ratio, maximal mid-expiratory flow rate (MMF), maximal expiratory flow at 50 and 25% of FVC (MEF50 and MEF25, respectively), ratio of MEF50 to MEF25 (MEF50/MEF25). Methods Spirometric parameters were extracted from the records of patients aged 15 years or older who underwent pulmonary function testing as a routine preoperative examination before non-cardiac surgery at the University of Tokyo Hospital. RCEXP was calculated in each patient from the slope of the descending limb of the MEFV curve using two points corresponding to MEF50 and MEF25. Airway obstruction was defined as an FEV1/FVC and FEV1 below the statistically lower limit of normal. Results We retrospectively analyzed 777 spirometry records, and 62 patients were deemed to have airway obstruction according to Japanese spirometric reference values. The cut-off value for RCEXP was 0.601 s with an area under the receiver operating characteristic curve of 0.934 (95% confidence interval = 0.898–0.970). RCEXP was strongly associated with FEV1/FVC, and was moderately associated with MMF and MEF50. However, RCEXP was less associated with MEF25 and MEF50/MEF25. Conclusions Our findings suggest that an RCEXP of longer than approximately 0.6 s can be linked to the presence of airway obstruction. Application of the concept of RCEXP to spontaneously breathing subjects was feasible, using our simple calculation method.

Spirometry flow-volume measurement is used routinely in the outpatient setting to rule out obstructive lung diseases. Biphasic flow-volume loop is a classic presentation of unilateral bronchial stenosis due to multiple etiologies and it should raise clinical suspicion. Granulomatosis with polyangiitis (GPA) is a systemic inflammatory condition with pulmonary manifestations that may be infiltrative (e.g., pneumonia), hemorrhagic, and may rarely cause bronchial stenosis. Herein, we present a case of GPA-related, bronchial obstruction that caused biphasic flow-volume loop along with a literature review.

Differences in the absolute flow and volume of maximal expiratory flow-volume (MEFV) curves have been studied extensively in health and disease. However, the shapes of MEFV curves have received less attention. We questioned if the MEFV curve shape was associated with (i) expiratory flow limitation (EFL) in health and (ii) changes in bronchial caliber in asthmatics. Using the slope-ratio (SR) index, we quantified MEFV curve shape in 84 healthy subjects and 8 matched asthmatics. Healthy subjects performed a maximal exercise test to assess EFL. Those with EFL during had a greater SR (1.15 ± 0.20 vs. 0.85 ± 0.20, p < 0.05) yet, there was no association between maximal oxygen consumption and SR (r = 0.14, p > 0.05). Asthmatics average SR was greater than the healthy subjects (1.35 ± 0.03 vs. 0.90 ± 0.11, p < 0.05), but there were no differences when bronchial caliber was manipulated. In conclusion, a greater SR is related to EFL and this metric could aid in discriminating between groups known to differ in the absolute size of MEFV curves.

Evaluation of novel compounds for COPD often relies on FEV1 for signal detection. Partial forced exhalations from end-tidal inspiration (PEFV) might complement FEV1 in identifying such a signal. We examined the prevalence of bronchodilator response (BDR) using PEFV and FEV1 in patients with COPD.110 consecutive COPD patients were tested prospectively with PEFV and maximal expiratory flow before and after inhalation of a short-acting β2 agonist (salbutamol, 400 μg). Partial flow at 800 ml above residual volume was derived from the PEFV (PF800). Significant changes in PF800 and/or FEV1 were set at the upper 95% confidence interval after placebo (n = 28).Four groups were identified by the presence (+) or absence (-) of a BDR: Group 1 [PF800 (-)FEV1(-)] when no change was observed (n = 31), Group 2 [PF800(+)FEV1(-)] when PF800 alone improved (n = 31), Group 3 [PF800(-)FEV1(+)] when FEV1 alone improved (n = 26), and Group 4 [PF800(+)FEV1(+)] when both variables improved (n = 18). There were 35 non-responders in any parameter, and 75/110 subjects who showed a response in at least one parameter. The changes in PF800 and FEV1 were not correlated suggesting these assess different airway generations.The use of PF800 increased detection of a BDR in COPD compared to FEV1 alone and may reflect small airway responses. The PEFV maneuver is simple, repeatable and may avoid some of the theoretical disadvantages of FEV1. The role of PF800 for evaluating novel anti-inflammatory agents remains to be determined.

Wei Wang, Mengshuang Xie, Shuang Dou, Liwei Cui, Wei Xiao Department of Pulmonary Medicine, Qilu Hospital, Shandong University, Jinan, People’s Republic of China Background: In a previous study, we demonstrated that asthma patients with signs of emphysema on quantitative computed tomography (CT) fulfill the diagnosis of asthma-COPD overlap syndrome (ACOS). However, quantitative CT measurements of emphysema are not routinely available for patients with chronic airway disease, which limits their application. Spirometry was a widely used examination tool in clinical settings and shows emphysema as a sharp angle in the maximum expiratory flow volume (MEFV) curve, called the “angle of collapse (AC)”. The aim of this study was to investigate the value of the AC in the diagnosis of emphysema and ACOS. Methods: This study included 716 participants: 151 asthma patients, 173 COPD patients, and 392 normal control subjects. All the participants underwent pulmonary function tests. COPD and asthma patients also underwent quantitative CT measurements of emphysema. The AC was measured using computer models based on Matlab software. The value of the AC in the diagnosis of emphysema and ACOS was evaluated using receiver-operating characteristic (ROC) curve analysis. Results: The AC of COPD patients was significantly lower than that of asthma patients and control subjects. The AC was significantly negatively correlated with emphysema index (EI; r=-0.666, P

Conventional spirometric parameters have shown poor correlation with symptoms and health status of chronic obstructive pulmonary disease (COPD). While it is well-known that the pattern of the expiratory flow-volume curve (EFVC) represents ventilatory dysfunction, little attempts have been made to derive quantitative parameters by analyzing the curve. In this study, we aimed to derive useful parameters from EFVC via graphic analysis and tried to validate them in patients with COPD.Using Graphical Analysis 3.4 Vernier Software, we derived from the EFVC such parameters as area of obstruction (Ao), area of triangle (AT), area of rectangle (AR) and ratio of volume at 75 and 25% peak expiratory flow (PEF) (0.25/0.75 V). For validation, we reviewed clinical and spirometric data of 61 COPD patients from Seoul National University Airway Registry (SNUAR) and Korean obstructive Lung Disease (KOLD) cohorts.Of all parameters, only RV/TLC significantly correlated with scores from St. George's Respiratory Questionnaire (SGRQ) (r = 0.447, p = 0.037). Six-minute walking distance (6MWD) highly correlated with Ao/AR (r = -0.618, p = 0.005) and Ao/PEF (r = -0.581, p = 0.009) whereas neither FEV1 nor FEV1/FVC had significant correlation with 6MWD.Ao/AR and Ao/PEF are promising parameters which correlate well with the exercising capacity of COPD patients.

Analysis of maximal expiratory flow-volume curves (MEFVCs) allows for determination of airway obstruction, but quantitative methods to describe these curves are not commonly used.We sought to determine the variability in MEFVC concavity assessment by pulmonary physicians, whether objective indices of concavity can be substituted for subjective expert impression, and whether MEFVC concavity correlates with clinical outcomes.A survey of 37 MEFVCs (plus 3 duplicates) was sent to pulmonologists for quantitative assessment of MEFVC concavity. Objective indices (β-angle, ratio forced expiratory flow at 50% of total lung volume to peak expiratory flow rate [FEF50/PEFR], ratio of maximum mid-expiratory flow to FVC [MMEF/FVC], kmax, and averaged flow-volume second derivatives) were calculated for each MEFVC and were correlated with the mean expert score. Both the mean expert scores and the best-performing index were then correlated with hospitalizations.Ninety-two respondents provided usable data. There was substantial variability in concavity scores between subjects, but strong intrasubject reliability. Mean expert score did not differ by physician years of experience. Several indices (β-angle, FEF50/PEFR, FEV1/FVC, MMEF/FVC, FEF50, and forced expiratory flow between 25 and 75% of total lung volume) correlated strongly with mean expert scores. A new variable (β-MMEF) was constructed using coefficients from stepwise linear regression and accurately predicted the mean expert score (R(2) = 0.96). Mean expert score and β-MMEF showed similar odds ratios for hospitalization (2.13 and 2.32, respectively) with identical positive (∼71%) and negative (87%) predictive values. The β-MMEF was also associated with hospitalizations in two independent cohorts of children with asthma and cystic fibrosis.The β-MMEF is an objective measure of maximal expiratory flow-volume curve concavity and highly correlates with expert impression. Both the mean expert score for expiratory curve concavity and the β-MMEF were associated with increased risk of subsequent hospitalization. The β-MMEF may be a useful biomarker for disease severity in asthma and cystic fibrosis.

Background Conventional spirometric parameters have shown poor correlation with symptoms and health status of chronic obstructive pulmonary disease (COPD). While it is well-known that the pattern of the expiratory flow-volume curve (EFVC) represents ventilatory dysfunction, little attempts have been made to derive quantitative parameters by analyzing the curve. In this study, we aimed to derive useful parameters from EFVC via graphic analysis and tried to validate them in patients with COPD. Methods Using Graphical Analysis 3.4 Vernier Software, we derived from the EFVC such parameters as area of obstruction (Ao), area of triangle (AT), area of rectangle (AR) and ratio of volume at 75 and 25 % peak expiratory flow (PEF) (0.25/0.75 V). For validation, we reviewed clinical and spirometric data of 61 COPD patients from Seoul National University Airway Registry (SNUAR) and Korean obstructive Lung Disease (KOLD) cohorts. Results Of all parameters, only RV/TLC significantly correlated with scores from St. George’s Respiratory Questionnaire (SGRQ) (r = 0.447, p = 0.037). Six-minute walking distance (6MWD) highly correlated with Ao/AR (r = −0.618, p = 0.005) and Ao/PEF (r = −0.581, p = 0.009) whereas neither FEV1 nor FEV1/FVC had significant correlation with 6MWD. Conclusions Ao/AR and Ao/PEF are promising parameters which correlate well with the exercising capacity of COPD patients. Electronic supplementary material The online version of this article (doi:10.1186/s12890-016-0182-8) contains supplementary material, which is available to authorized users.

The American Thoracic Society (ATS) and European Respiratory Society (ERS) emphasize a satisfactory start in maximal expiratory flow-volume (MEFV) curves and highlight subjective parameters: performance without hesitation and expiration with maximum force. We described a new parameter, angle β for characterization of the start to the MEFV curve.Subjects completed the MEFV curve at least three times and at least two curves met ATS/ERS quality. Subjects were divided into normal, restrictive and obstructive groups according to pulmonary function test results. The tangent line was drawn at the start of the MEFV curve's ascending limb to the x-axis and the angle β between the tangent line and x-axis was obtained. The relationships between tangent of β, pulmonary function parameters (PFPs) and anthropometric data were assessed. The MEFV curves with insufficient explosion at the start were considered as poor-quality MEFV curves.In 998 subjects with high-quality spirometry, although PFP varied in relation to the three aspects: the angle β and its tangent were similar (P 0.05), the tangent of β did not correlate with PFP or anthropometric measurements (P 0.05) and the lower limit of normal (LLN) of the angle β was 80° in the group with high-quality spirometry (P 0.05). Angle β derived from poor-quality MEFV curves was smaller than that from good quality one (P 0.05).Angle β may function as a parameter to assess the expiratory efforts, which can be used to assess the quality of the MEFV curve start.

We obtained flow-volume (F-V) curves in anesthetized rats by applying positive pressure on the body surface. To obtain the best curve, tracheal intubation with either a 12 or 13 gauge catheter and a surface pressure greater than 56 cmH(2)O was necessary. Peak expiratory flow rate (PEFR) and forced vital capacity (FVC) were shown to be optimal parameters for estimation of bronchoconstriction induced by methacholine inhalation while FEV(0.05) (forced expiratory volume at 0.05 s) and FEV(0.10) were of limited usefulness for this purpose. The descending segment of the F-V curve consisted of two or three phases, with later phases shortened during bronchoconstriction. In conclusion, PEFR and FVC are optimal parameters for estimation of bronchoconstriction in rats. The decreases in PEFR and FVC may reflect constriction in large and smaller airways, respectively.

Flow limitation in the airways is a fundamental process constituting the maximal expiratory flow-volume curve. Its location is referred to as the choke point. In this work, expressions enabling the calculation of critical flows in the case of wave-speed, turbulent or viscous limitation were derived. Then a computational model for the forced expiration from the heterogeneous lung was used to analyse the regime and degree of flow limitation as well as movement and arrangement of the choke points. The conclusion is that flow limitation begins at similar time in every branch of the bronchial tree developing a parallel arrangement of the choke points. A serial configuration of flow-limiting sites is possible for short time periods in the case of increased airway heterogeneity. The most probable locations of choke points are the regions of airway junctions. The wave-speed mechanism is responsible for flow choking over most of vital capacity and viscous dissipation of pressure for the last part of the test. Turbulent dissipation, however, may play a significant role as a supporting factor in transition between wave-speed and viscous flow limitation.

To assess the quality control for the maximal expiratory flow-volume (MEFV) curve in school-age children.Eight hundred and sixty-two children who had two or more MEFV manoeuvres were classified into ≥6-year-old (n=379), ≥8-year-old (n=210), ≥10-year-old (n=64), and 12-17-year-old groups (n=109). The parameters of quality control and concordance with quality control criteria for MEFV were compared between the two groups. In addition, patients who were diagnosed with asthma were classified into two groups, one with normal pulmonary function (n=155) and the other with abnormal pulmonary function (n=62), based on the results of spirometry. Differences in the parameters of quality control for spirometry were compared between the two groups.Eight hundred and sixty-two children underwent 2 367 MEFV manoeuvres, 97.8% of which met the start of test criterion for backward extrapolated volume (VBE) of less than 0.15 L, with the highest concordance in the ≥6-year-old group and the lowest concordance in the 12-17-year-old group. Three hundred and eighty-one children (44.2%) met the end of test criterion for forced expiratory time (FET) and the concordance in children over 10 years of age was lower than that in children under 10 years of age (P0.05). Differences in two best forced expiratory volume in first second (FEV1) and forced vital capacity (FVC) manoeuvres were within 150 mL in 91.9% and 84.8%, respectively, of the children. The parameters of quality control for spirometry were better for asthmatic children with abnormal pulmonary function compared with asthmatic children with normal pulmonary function (P0.05).Concordance with the start of test criteria and the manoeuvre repeatability criteria is high, whereas the concordance with the end of test criteria is low. It is suggested that the concordance with the FET criteria should be improved.

The jet nebulizer is a common device used for administering aerosol medication in young children. However, compared to a metered dose inhaler-spacer (MDI-spacer), it takes more time and personnel. This study aimed to compare the efficacy of salbutamol aerosol therapy given via these two devices in young wheezing children. A prospective randomized, double-blind, placebo-controlled trial was performed in children up to 5 years old who had acute wheezing and were admitted to the Department of Pediatrics, King Chulalongkorn Memorial Hospital. Patients were randomly divided into two groups. The first group received 2 puffs of placebo via MDI-spacer, followed by 0.15 mg/kg salbutamol respiratory solution via jet nebulizer. The second group received 2 puffs (100 microg/puff) of salbutamol via MDI-spacer, followed by placebo via jet nebulizer. Clinical scores and tidal breathing pulmonary function test were evaluated before and after treatment. Pulmonary function parameters included those derived from flow volume loops (volume to peak tidal expiratory flow over total expiratory volume, V(PTEF)/V(E); time to peak tidal expiratory flow over total expiratory time, T(PTEF)/T(E); and ratio of tidal expiratory flow at 25% remaining expiration to peak expiratory flow, 25/PF), compliance (Crs), and resistance (Rrs) of the respiratory system. The efficacy of both methods was compared by using analysis of covariance. Forty-seven wheezing children were studied (24 received salbutamol via MDI-spacer, and 23 received it via jet nebulizer). There was no statistical difference between the two groups regarding clinical scores and all pulmonary function parameters. However, heart rate was significantly increased after treatment in the jet nebulizer group when compared to those in the MDI-spacer group (P = 0.004). In conclusion, the efficacy of salbutamol aerosol therapy via MDI-spacer compared to jet nebulizer in young wheezing children was not different in terms of clinical score and postbronchodilator pulmonary function parameters. However, salbutamol aerosol therapy via jet nebulizer significantly increased the heart rate when compared to the MDI-spacer.

Nasal continuous positive airway pressure (nCPAP) has been widely established in the treatment of obstructive sleep apnea syndrome (OSAS). However, only few studies have evaluated long-term effects of this treatment on lung function. This study assesses the effect of nCPAP on lung function parameters and response to bronchodilators in 50 OSAS patients. Spirometry and arterial blood gas measurements were performed before starting nCPAP and after 16.8 +/- 8 months of treatment. Of the 50 study patients (55 +/- 12 years, with an apnea/hypopnea index of 47 +/- 34h(-1)), 15 had asthma, 13 had chronic obstructive pulmonary disease (COPD) and 22 had no obstructive airway disease (NOAD). In the entire population, significant decreases in FEF50 (from 69 +/- 38% to 61 +/- 30%, P0.005), FEF25 (from 53 +/- 34% to 46 +/- 28%, P0.05) and FEF25-75 (from 65 +/- 33% to 57 +/- 27%, P0.005) were observed after treatment. No impairment of lung function was found in COPD and asthmatic patients. In contrast, lung function was changed in the NOAD group where FEF50, FEF25 and FEF25-75 as well as FEV1 and FEV1/VC ratio were significantly reduced. Moreover, bronchial hyperresponsiveness occurred in five of 22 patients of this group. These results suggest that tolerance of nCPAP should be handled by long-term follow-up of flow-volume loops.

Studies of airway function during exercise have produced conflicting results both in healthy and diseased subjects. Respiratory resistance (Rrs) was measured using an impulse oscillation technique. A flow/resistance curve was established for each of 16 healthy males during voluntary hyperventilation (VHV) at rest. Then, Rrs and flow were measured immediately (t(0)) and 90 sec (t(90)) after exercise on a cycle ergometer at 60, 70, and 80% of maximal aerobic power. The flow/resistance relationship at rest during VHV was used to assess the flow dependence of Rrs. Rrs at t(0) was higher than at rest (P0.01) but lower than Rrs obtained at matched flow during VHV (P0.05). In healthy subjects, the linear increase in Rrs with VHV indicates airflow dependency of Rrs following Rohrer's equation. The relative decrease in Rrs with exercise suggests bronchodilation. The bronchodilating effect disappeared promptly when exercise was stopped suggesting that it may have been related to a reflex mechanism.

Recently, it has been suggested that peak expiratory flow (PEF) may be determined by the wave speed flow-limiting mechanism. In six normal male subjects (age = 33 +/- 8 years) performing expiratory forced vital capacity (FVC) maneuvers, a negative expiratory pressure (NEP) of -10 cm H2O was randomly applied at the beginning of maximal expiration to assess changes in PEF as compared with baseline. During FVC maneuvers, the expiratory effort was measured by changes in esophageal pressure (Pes), as either peak expiratory Pes-Pes at end expiratory lung volume (DeltaPes(peak)) or maximal rate of rise of Pes (dPes/dt(max)). In each experimental condition, at least three FVC maneuvers with comparable expiratory effort were selected for analysis for each subject. With similar DeltaPes(peak) (107.2 +/- 34.9 versus 111.7 +/- 40.5 cm H2O) and dPes/dt(max) (1181 +/- 518 versus 1177 +/- 546 cm H2O/second) PEF amounted to 10.84 +/- 1.08 L/second and to 10.82 +/- 1.03 L/second with and without NEP, respectively. These data show that PEF obtained by normal subjects to the best of their abilities (best PEF) does not increase with NEP and indicate that the best PEF is a flow-limited and effort-independent parameter, reflecting only lung and airways mechanics as the other subsequent maximal expiratory flows achieved during the FVC maneuver.

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.

Duchenne's muscular dystrophy (DMD), characterized by gradually developing muscular weakness, leads to respiratory symptoms and reduced lung function. We aimed to assess lung function in 25 patients with DMD in relationship to age and muscular function. The 25 boys, mean age 13 years, comprized patients in southern Norway with DMD, taking part in an epidemiological follow-up study. None had chronic respiratory disease. Lung function was measured by maximum expiratory flow–volume loops and whole body plethysmography, and repeated after 1 year ( n =14). Lung function was reduced compared to predicted values for healthy children. Forced expiratory volume in 1 sec (FEV 1 )% predicted and forced vital capacity (FVC)% predicted correlated (significantly) inversely to age. FEV 1 and FVC decreased annually 5·61 and 4·2% of predicted, respectively. Absolute values of FVC (litres) and FEV 1 (l sec −1 ) increased until mean age 14 years, decreasing thereafter. Values in % predicted decreased steadily throughout the age range (6–19 years). Lung function correlated closely to upper limb muscle function.

The aim of this study was to evaluate the applicability of American Thoracic Society and European Respiratory Society criteria for spirometry in children.Maximal expiratory flow/volume (MEFV) measurements from 446 school-age children, experienced in performing MEFV manoeuvres, were studied and acceptability (start-of-test (backward extrapolated volume as a percentage of forced vital capacity (FVC) (Vbe%FVC) or as an absolute value (Vbe), end-of-test (forced expiratory time (FET)) and reproducibility criteria (absolute and percentage difference between best and second-best FVC and forced expiratory volume in one second (FEV1) (ΔFVC, ΔFVC %, ΔFEV1and ΔFEV1%)) were applied to these manoeuvres.TheVbe%FVC criterion was met by 91.5%, theVbeVbeVbeVbe%FVC. The FET criterion was met by only 15.3% of children. ΔFVC 111%). Even experienced children did not meet all international criteria for spirometry. However, most of their MEFV curves are useful for interpretation.Based on the performance of these children, a re-evaluation of criteria for maximal expiratory flow/volume measurements in children is proposed.

Inhaled beta2-agonists have been subject to restrictions in relationship to sports due to fear of possible improvement in endurance performance. According to the international doping regulations only inhaled salbutamol, terbutaline and salmeterol are allowed for use in sports. Formoterol is a recently introduced rapid onset-long-acting inhaled beta2-agonist. The main aim of the present randomized, double-blind placebo-controlled study was to investigate possible improvement in endurance performance of inhaled formoterol in 24 healthy well-trained competitive male athletes, 21-29 years old. Lung function (flow-volume loops) was measured before, 15 min after each inhaled study drug and before and repeatedly after exercise. On day 1, maximum oxygen uptake (VO2max), peak ventilation (VEpeak) and running time till exhaustion were measured and used to determine the exercise load on days 2 and 3. On days 2 and 3 the subjects inhaled the study drugs, rested for 1 h, then exercised, and VO2max, VEpeak and running time until exhaustion were determined. Inhaled formoterol did not improve any parameter of endurance performance. On the other hand a statistically significant, although not clinically significant (0.05 ml(-1) min kg(-1)), change was found in estimated difference of VO2max between formoterol and placebo in favour of placebo. Lung function increased significantly after inhaled formoterol, and after exercise also for placebo, but without differences between the beta2-agonist and placebo after exercise. In conclusion, inhaled formoterol did not improve endurance performance compared to placebo.

We have measured bronchial responsiveness (BR) to histamine on two occasions between 5 and 24 h apart, to determine if conventional and new indices of BR are repeatable. A random sample of 29 healthy male subjects with a mean age of 19 (SD 3.44) years from a larger study repeated a Yan method test of BR, recording both partial and maximal expiratory flow volume (PEFV and MEFV) curves. From the MEFV curves log-dose slopes (LDS) for forced expiratory volume in 1 sec (FEV1), forced expiratory flow between 25% and 75% of forced vital capacity (FVC) (FEF(25-75%)), mean expiratory flow at 30% and 40% of FVC (MEF30, MEF40), and the first moment of the spirogram (alpha1) truncated at 75% and 90% of FVC were calculated, as well as the provocative dose that induces a 20% fall in FEV1 (PD20FEV1). From the PEFV curves LDS for alpha(1)75% and alpha(1)90%, and MEF30 and MEF40 were derived. Apart from MEF30 and alpha(1)90% the second test was significantly lower (P

Background Vocal cord dysfunction can coexist with or masquerade as asthma. Vocal cord dysfunction, when coexistent with asthma, contributes substantially to the refractory nature of the respiratory problem. Objective To report a case of an asthmatic patient with vocal cord dysfunction and a previously unreported unique expiratory flow volume curve. Results A 16-year-old female, known to have asthma, developed increased frequency of her asthma exacerbations. Spirometry, during symptoms, showed an extrathoracic airway obstruction with a reproducible unique abrupt drop and rise in the expiratory flow volume loop. Laryngoscopy showed adduction of the vocal cords during inspiration and expiration. Conclusions We report a unique expiratory flow volume curve in an asthmatic with vocal cord dysfunction that resolved with panting maneuvers. Speech and psychological counseling helped prevent future attacks.