Interventional bronchoscopy for chronic obstructive pulmonary disease: more than a pipe dream.

Endoscopic lung volume reduction (ELVR) is recognised in both national and international expert guidelines as one of the few additive treatments to benefit patients with advanced chronic obstructive pulmonary disease (COPD) who are otherwise receiving optimal medical and supportive care. Despite these recommendations and a growing evidence base, these procedures are not widely offered across Australia and New Zealand, and general practitioner and physician awareness of this therapy can be improved. ELVR aims to mitigate the impact of hyperinflation and gas trapping on dyspnoea and exercise intolerance in COPD. Effective ELVR is of proven benefit in improving symptoms, quality of life, lung function and survival. Several endoscopic techniques to achieve ELVR have been developed, with endobronchial valve placement to collapse a single lobe being the most widely studied and commonly practised. This review describes the physiological rationale underpinning lung volume reduction, highlights the challenges of patient selection, and provides an overview of the evidence for current and investigational endoscopic interventions for COPD.

[A study on the end criteria of forced vital capacity curve in adults].

Objective: To explore the end criteria of forced vital capacity(FVC) curve in adults. Methods: A multicenter cross-sectional study was performed in Zhongshan Hospital Affiliated to Fudan University, the First Affiliated Hospital of Fujian Medical University, and the Third Affiliated Hospital of Inner Mongolia Medical University from January 2017 to August 2017. A consecutive sample of subjects who completed the spirometry test and FVC curves met end criteria of no volume change (<0.025 L) for ≥ 1 s were qualified in this study. Subjects were divided into a normal group (n=610), an obstructive group (n=536), and a restrictive group(n=306) according to pulmonary function test results. The FET values in different groups were compared. The side effects in the 3 groups and the diagnostic accuracy, specificity and security of different FET in the obstructive group were assessed. Results: The FET values of the normal group, the obstructive group, and the restricted group were (4.00±1.07) s, (8.08±1.56) s and (2.97±0.76) s respectively, and the 95% CI of FET in the 3 groups were between 3.88-4.12 s, 7.02-10.14 and 2.21- 3.73 s (F=2 263.80, P<0.01). When the exhalation platform was used as the standard of FVC curve, the adverse reaction rate in the normal group and the restricted group were 1.1% and 1.3% respectively, lower than the rate of 17.2% in the obstructive group (χ(2)=92.73, χ(2)=48.49 respectively; all P<0.05). In the obstructive group, 7 s as the ending criterion had similar incidence of adverse reactions to 6 s (χ(2)=0.01, P=0.93). With further extension of expiration time, the incidence of adverse reactions increased significantly. In the obstructive group, the sensitivity of FEV(1)/FEV(7) was 99.25%, higher than that at FEV(1)/FEV(6) (χ(2)=4.06, P=0.04), and the specificity of diagnosis was very similar and 100%. Conclusions: FET was variable in subjects with different lung function status. It is not appropriate to use a fixed FET≥ 6 s as the end criterion of spirometry for adults. For patients with normal lung function or restrictive lung function defect, exhalation platform should be used as the end of exhalation standard. For patients with obstructive lung function defect, an FET of up to 7 s is appropriate.

Quantitative CT-based structural alterations of segmental airways in cement dust-exposed subjects.

BACKGROUND: Dust exposure has been reported as a risk factor of pulmonary disease, leading to alterations of segmental airways and parenchymal lungs. This study aims to investigate alterations of quantitative computed tomography (QCT)-based airway structural and functional metrics due to cement-dust exposure. METHODS: To reduce confounding factors, subjects with normal spirometry without fibrosis, asthma and pneumonia histories were only selected, and a propensity score matching was applied to match age, sex, height, smoking status, and pack-years. Thus, from a larger data set (N = 609), only 41 cement dust-exposed subjects were compared with 164 non-cement dust-exposed subjects. QCT imaging metrics of airway hydraulic diameter (Dh), wall thickness (WT), and bifurcation angle (θ) were extracted at total lung capacity (TLC) and functional residual capacity (FRC), along with their deformation ratios between TLC and FRC. RESULTS: In TLC scan, dust-exposed subjects showed a decrease of Dh (airway narrowing) especially at lower-lobes (p < 0.05), an increase of WT (wall thickening) at all segmental airways (p < 0.05), and an alteration of θ at most of the central airways (p < 0.001) compared with non-dust-exposed subjects. Furthermore, dust-exposed subjects had smaller deformation ratios of WT at the segmental airways (p < 0.05) and θ at the right main bronchi and left main bronchi (p < 0.01), indicating airway stiffness. CONCLUSIONS: Dust-exposed subjects with normal spirometry demonstrated airway narrowing at lower-lobes, wall thickening at all segmental airways, a different bifurcation angle at central airways, and a loss of airway wall elasticity at lower-lobes. The airway structural alterations may indicate different airway pathophysiology due to cement dusts.

Clinical significance of lower-lobe interstitial lung disease on high-resolution computed tomography in patients with idiopathic pleuroparenchymal fibroelastosis.

BACKGROUND: Idiopathic pleuroparenchymal fibroelastosis (IPPFE) is a rare form of idiopathic interstitial pneumonias (IIP) and may have other patterns of interstitial lung disease (ILD) in the lower lobe, such as usual interstitial pneumonia (UIP). However, the clinical significance of lower-lobe ILD in patients with IPPFE is unclear. METHODS: A retrospective review of 40 consecutive patients with clinically diagnosed IPPFE in our institution from 2005 to 2016 was conducted. The presence of lower-lobe ILD on high-resolution computed tomography (HRCT) was assessed and classified into UIP or non-UIP pattern according to a modification of diagnostic criteria for idiopathic pulmonary fibrosis. Clinical characteristics and prognostic factors were evaluated. RESULTS: Among the 40 patients with IPPFE, 21 (53%) had lower-lobe ILD, including 13 with UIP pattern and 8 with non-UIP pattern. Patients with IPPFE who had lower-lobe ILD had significantly older age, higher frequency of fine crackles, higher serum KL-6 level, lower residual volume (RV), and lower total lung capacity (TLC) than those without lower-lobe ILD. In addition, those with lower-lobe ILD, especially UIP pattern, had a significantly poorer survival than those without lower-lobe ILD (log-rank test; p = 0.014, p < 0.001, respectively). Multivariate Cox proportional hazards regression analysis revealed that low %forced vital capacity (%FVC) at baseline and coexistence of UIP pattern were significantly associated with poor prognosis in patients with IPPFE. CONCLUSIONS: The coexistence of lower-lobe ILD on HRCT, especially the UIP pattern, may predict poor survival in patients with IPPFE.

Inspiratory muscle training improves pulmonary functions and respiratory muscle strength in healthy male smokers.

The aim of the present study is to investigate the effects of inspiratory muscle training (IMT) on pulmonary function and respiratory muscle strength of both healthy smokers and nonsmokers. Forty-two healthy males (16 in the IMT smokers group [IMTS], 16 in the IMT nonsmokers group [IMTN], and 10 in the placebo group) participated in the present study. Using a randomized, double-blind, placebo-controlled design, IMTS and IMTN underwent 4 weeks of 30 breaths twice daily at 50% (+5% increase each week) of maximum inspiratory pressure (MIP), while the placebo group maintained 30 breaths twice daily at 15% MIP using an IMT device. The data were analyzed with repeated measures for one-way analysis of variance, 3 × 2 mixed factor analysis of variance, and least significant difference tests. Respiratory muscle strength (MIP and maximal expiratory pressure [MEP]) and pulmonary functions significantly improved after a 4-week period (between the pre and posttests) in the IMTN and IMTS groups (p < 0.05). The mean difference and percentage differences showed significant alterations in the respiratory muscle strength, forced and slow pulmonary capacities, and pulmonary volume between the IMTN and IMTS groups (p < 0.05). There were significant changes in the expiratory muscle strength (MEP), slow vital capacity (SVC), and forced pulmonary measurements (forced expiratory volume after 1 s and maximal voluntary ventilation) between IMTN and IMTS groups in favor of smokers (p < 0.05). These results show that greater improvements occurred in smokers after IMT. Increased respiratory muscle strength may be the underlying mechanism responsible for this improvement. Additionally, the benefits of IMT were greater in smokers than nonsmokers. This difference between smokers and nonsmokers may potentially be explained by higher influence of exercise on smokers' lung microbiome, resulting in greater reversal of negative effects.

Clinical characteristics and outcomes of hypersensitivity pneumonitis: a population-based study in China.

BACKGROUNDS: Hypersensitivity pneumonitis (HP) is an immune-mediated interstitial lung disease (ILD) that develops in response to the inhalation of various antigens. The clinical pathologies are very complex and undetermined. The clinical features and outcomes of HP have not been fully elucidated. The aim of this study was to analyze the incidence, clinical features, and outcomes of HP patients and construct a simple clinical model for diagnosing chronic HP (CHP). METHODS: The cohort study included 101 patients with HP admitted to the Nanjing Drum Tower Hospital from January 2009 to December 2017. The patients were categorized into acute HP (AHP, n = 72) and CHP (n = 29) groups according to the updated international criteria. The clinical, imaging, treatment, and follow-up data were retrospectively reviewed. All patients were followed up until December 31, 2017. Statistical analysis was performed, and a clinical scoring system for CHP was constructed by SPSS 20.0 software. RESULTS: The incidence of HP was 2.4% in ILD inpatients in our center. Patients in the CHP group were older (t = -2.212, P = 0.029), had more smokers (χ = 8.428, P = 0.004), and longer duration of symptoms (t = -4.852, P < 0.001) than those in the AHP group. Weight loss, crackles, digital clubbing, and cyanosis were more common in the CHP group than those in the AHP group (χ = 5.862, P < 0.001; χ = 8.997, P = 0.003; χ = 11.939, P = 0.001; and χ = 4.025, P = 0.045, respectively). On chest high-resolution computed tomography (HRCT), reticular patterns, traction bronchiectasis, and accompanying honeycombing were more common in CHP cases than those in AHP cases (χ = 101.000, P < 0.001; χ = 32.048, P < 0.001; and χ = 36.568, P < 0.001, respectively). The clinical scoring system for CHP was established based on the clinical variables (age [A], duration of symptoms [D], smoking history [S], unidentified exposure [U], and chest HRCT [C]; ADSUC) (area under the curve 0.935, 95% confidence interval: 0.883-0.987, P < 0.001). Eleven patients (15.3%) in the AHP group developed CHP, and unidentified exposure was an independent risk factor for the progression of disease (P = 0.038). The survival of patients with CHP, smoking history, unidentified antigens and fibrosis on Chest HRCT were significantly worse (P = 0.011, P = 0.001, P = 0.005, and P = 0.011, respectively) by Kaplan-Meier analysis. Cox multivariate regression analysis revealed that unidentified exposure and total lung volume (TLC pred%) were independent prognostic predictors for HP patients (P = 0.017 and P = 0.017, respectively). CONCLUSIONS: The clinical features and outcomes of the CHP patients differ from those of the AHP patients. ADSUC is a simple and feasible clinical model for CHP. Unidentified exposure is an independent risk factor for the progression of AHP to CHP. Unidentified exposure and a low baseline TLC pred% are independent predictors for survival in HP patients.

Lung CT Densitometry in Idiopathic Pulmonary Fibrosis for the Prediction of Natural Course, Severity, and Mortality.

BACKGROUND: In this study, we retrospectively assessed the relationships among physiologic measurements, survival, and quantitative high-resolution CT (HRCT) scanning indexes in patients with idiopathic pulmonary fibrosis (IPF). METHODS: Seventy patients (48 male; mean [SD] age, 66.4 [9.0] years) with IPF were enrolled in the study. After segmentation of the lungs in thin-section CT scanning with the patient in the supine position at full inspiration, we assessed following parameters: mean lung attenuation (MLA), skewness, kurtosis, peak attenuation, total lung area, inflexion point with slope, and area right of the inflexion point (AROIP). Additionally, FVC, FEV1, total lung capacity, diffusing capacity or transfer factor of the lung for carbon monoxide (Dlco), and 6-min walk distance were analyzed. Univariate and multivariate analysis were used for the prediction of physiologic outcomes by HRCT scanning indexes and then were correlated to survival in a proportional hazards analysis. RESULTS: The strongest correlation was observed between MLA and FEV1, with an r of -0.63. MLA, peak attenuation, slope, attenuation, and AROIP correlated negatively with all physiologic measurements. AROIP was the best predictor of Dlco. Analysis for prediction of mortality showed that AROIP, kurtosis, and FVC were related significantly to survival. Multivariate regression revealed a significant impact of only AROIP (among age, sex, MLA, skewness, kurtosis, FVC, and Dlco) on survival. CONCLUSIONS: These data indicate that HRCT scanning indexes are correlated to physiologic measurements. The newly defined parameter, AROIP, is of additive value for prediction of outcome. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT02951416; URL: www.clinicaltrials.gov.

The effects of five days of intensive preoperative inspiratory muscle training on postoperative complications and outcome in patients having cardiac surgery: a randomized controlled trial.

OBJECTIVE: To determine the prophylactic efficacy of short-term intensive preoperative inspiratory muscle training on the incidence of postoperative pulmonary complications in patients scheduled for cardiac surgery. DESIGN: Single-blind, randomized controlled pilot study. SETTING: TEDA International Cardiovascular Hospital, China. SUBJECTS: In total, 197 subjects aged ⩾50 years scheduled for cardiac surgery were selected. INTERVENTION: The intervention group ( n = 98) received five days of preoperative inspiratory muscle training on top of the usual care received by the patients in the control group ( n = 99). MAIN MEASURES: The primary outcome variable was the occurrence of postoperative pulmonary complications. The secondary outcome variables were inspiratory muscle strength, lung function and length of hospitalization. RESULTS: After cardiac surgery, a total of 10 (10.2%) of the 98 patients in the intervention group and 27 (27.3%) of 99 patients in the control group had postoperative pulmonary complications (risk ratio, 0.23; 95% confidence interval (CI), 0.09-0.58, P = 0.002). The study revealed that, compared with the control group, the intervention group had a significant increase in inspiratory muscle strength (by 10.48 cm H2O, P < 0.001), forced expiratory volume in the first second of expiration (FEV1) %predicted (by 3.75%, P = 0.030), forced vital capacity (FVC) %predicted (by 4.15%, P = 0.008) and maximal voluntary ventilation (MVV) %predicted (by 6.44%, P = 0.034). Length of hospital stay was 7.51 (2.83) days in the intervention group and 9.38 (3.10) days in the control group ( P = 0.039). CONCLUSION: A five-day intensive pattern of preoperative inspiratory muscle training reduced the incidence of postoperative pulmonary complications and duration of postoperative hospitalization in patients undergoing cardiac surgery.

Efficacy and Safety of Pirfenidone in Advanced Idiopathic Pulmonary Fibrosis.

BACKGROUND: Although phase 3 trials showed significant efficacy and acceptable safety profiles for pirfenidone in mild-to-moderate idiopathic pulmonary fibrosis (IPF), data on advanced IPF are limited. OBJECTIVES: The study aimed to evaluate the efficacy and safety of pirfenidone in advanced IPF patients. METHODS: The clinical data of 138 IPF patients (advanced group: 27%) treated with pirfenidone were retrospectively reviewed and compared between advanced and non-advanced groups. Advanced IPF was defined as (1) forced vital capacity (FVC) < 50% predicted or (2) diffusing capacity for carbon monoxide < 30% predicted. RESULTS: The mean treatment duration was 51.3 weeks, and lung function analysis was performed in 81 patients (17 in the advanced group). Changes in FVC and total lung capacity (TLC) were significantly reduced at 6 months after treatment in both the advanced (ΔFVC [6 months]: -6.3 [before] vs. 0.7% predicted [after]; ΔTLC: -5.3 vs. 0.8) and non-advanced (ΔFVC: -3.4 vs. 0.5; ΔTLC: -3.1 vs. -0.9) groups. The rate of decline in FVC and TLC was significant before treatment, but not after treatment in the advanced (FVC: -1.27 [before] vs. 0.21% predicted/month [after]; TLC: -0.89 vs. -0.15) and non-advanced (FVC: -0.60 vs. -0.20; TLC: -0.54 vs. -0.17) groups. The advanced group showed a similar rate of adverse events (AEs) (78.4 vs. 88.1%, p = 0.270), but more serious AEs (40.5 vs. 10.9%, p < 0.001) including death (24.3 vs. 5.0%, p = 0.002). CONCLUSIONS: In advanced IPF, pirfenidone showed similar efficacy and safety to non-advanced IPF except for serious AEs, which may be due to the advanced status itself.

CT-lung volume estimates in trauma patients undergoing stabilizing surgery for flail chest.

AIM: To estimate and compare lung volumes from pre- and post-operative computed tomography (CT) images and correlate findings with post-operative lung function tests in trauma patients with flail chest undergoing stabilizing surgery. PATIENTS AND METHODS: Pre- and post-operative CT images of the thorax were used to estimate lung volumes in 37 patients who had undergone rib plate fixation at least 6 months before inclusion for flail chest due to blunt thoracic trauma. Computed tomography lung volumes were estimated from airway distal to each lung hilum by outlining air-filled lung tissue either manually in images of 5 mm slice thickness or automatically in images of 0.6 mm slice thickness. Demographics, pain, range of motion in the thorax, breathing movements and Forced Vital Capacity (FVC) were assessed. Total Lung Capacity (TLC) measurements were also made in a subgroup of patients (n = 17) who had not been intubated at time of the initial CT. Post-operative CT lung volumes were correlated to FVC and TLC. RESULTS: Patients with a median age of 62 (19-90) years, a median Injury Severity Score (ISS) of 20 (9-54), and a median New Injury Severity Score (NISS) of 27 (17-66) were enrolled in the study. Median follow-up time was 3.9 (0.5-5.6) years. Two patients complained of pain at rest and when breathing. Pre-operative CT lung volumes were significantly different (p < 0.0001) from post-operative CT lung volumes, 3.51 l (1.50-6.05) vs. 5.59 l (2.18-7.78), respectively. At follow-up, median FVC was 3.76 l (1.48-5.84) and median TLC was 6.93 l (4.21-8.42). Post-operative CT lung volumes correlated highly with both FVC [rs = 0.75 (95% CI 0.57‒0.87, p < 0.0001)] and TLC [rs = 0.90 (95% CI 0.73‒0.96, p < 0.0001)]. The operated thoracic side showed decreased breathing movements. Range of motion in the lower thorax showed a low correlation with FVC [rs = 0.48 (95% CI 0.19‒0.70, p = 0.002)] and a high correlation with TLC [rs = 0.80 (95% CI 0.51‒0.92, p < 0.0001)]. CONCLUSIONS: Post-operative CT-lung volume estimates improve compared to pre-operative values in trauma patients undergoing stabilizing surgery for flail chest, and can be used as a marker for lung function when deciding which patient with chest wall injuries can benefit from surgery.

Bilateral Lung Transplantation and Simultaneous Pectus Excavatum Correction Using the Nuss Technique.

Severe chest wall deformities are considered a contraindication for lung transplantation. A 38-year-old man with idiopathic pulmonary fibrosis and severe pectus excavatum with a Haller index of 4.3 was considered eligible and listed for lung transplantation. Bilateral sequential transplantation and simultaneous correction of the pectus excavatum were performed via anterolateral thoracotomies and Nuss bar insertion with peripheral femorofemoral venoarterial extracorporeal membrane oxygenation support. Total lung capacity increased from 4.1 L preoperative to 5.8 L postoperative. This case demonstrates that a combined approach is feasible with good functional outcome.

Reference values for pulmonary volumes by plethysmography in a Brazilian sample of white adults / Valores de referência para volumes pulmonares por pletismografia em uma amostra brasileira de adultos da raça branca

ABSTRACT Objective: To derive reference values for healthy white Brazilian adults who have never smoked and to compare the obtained values with reference values derived by Crapo and by Neder. Methods: Reference equations by quantile regressions were derived in 122 men and 122 women, non-obese, living in seven cities in Brazil. Age ranged from 21 to 92 years in women and from 25 to 88 years in men. Lung function tests were performed using SensorMedics automated body plethysmographies according ATS/ERS recommendations. Lower and upper limits were derived by specific equations for 5 and 95 percentiles. The results were compared to those suggested by Crapo in 1982, and Neder in 1999. Results: Median values for total lung capacity (TLC) were influenced only by stature in men, and by stature and age in women. Residual volume was influenced by age and stature in both genders. Weight was directly related to inspiratory capacity and inversely with functional residual capacity and expiratory reserve volume in both genders. A comparison of observed TLC data with values predicted by Neder equations showed significant lower values by the present data. Mean values were similar between data from present study and those derived by Crapo. Conclusion: New predicted values for lung volumes were obtained in a sample of white Brazilians. The values differ from those derived by Neder, but are similar to those derived by Crapo.

RESUMO Objetivo: Derivar valores de referência para brasileiros adultos brancos saudáveis que nunca fumaram e comparar os valores obtidos com os valores de referência derivados por Crapo e por Neder. Métodos: Equações de referência por regressões quantílicas foram derivadas em 122 homens e 122 mulheres, não obesos, em sete cidades do Brasil. A idade variou entre 21 e 92 anos nas mulheres e de 25 a 88 anos nos homens. Os volumes pulmonares foram medidos por pletismógrafo de corpo automatizados SensorMedics, de acordo com as recomendações da SBPT e ATS/ERS. Os limites inferior e superior, expressos pelo percentil 5 e 95, foram derivados por equações específicas. Os resultados foram comparados aos sugeridos por Crapo em 1982 e Neder em 1999. Resultados: Os valores medianos para a capacidade pulmonar total (CPT) foram influenciados apenas pela estatura nos homens, e pela estatura e idade nas mulheres. O volume residual foi influenciado pela idade e estatura em ambos os sexos. O peso se correlacionou diretamente com a capacidade inspiratória e inversamente com a capacidade residual funcional e com o volume de reserva expiratório em ambos os sexos. A CPT observada, comparada com os valores previstos pela equação de Neder, foi significativamente menor. Os valores médios foram semelhantes entre os dados do presente estudo e os de Crapo. Conclusões: Novos valores previstos para os volumes pulmonares foram obtidos em uma amostra de brasileiros de raça branca. Os valores diferem daqueles derivados por Neder, mas são semelhantes aos derivados por Crapo.

Infant Pulmonary Function Testing and Phenotypes in Severe Bronchopulmonary Dysplasia.

BACKGROUND: The definition of severe bronchopulmonary dysplasia (sBPD) is based on respiratory support needs. The management of a patient with sBPD remains empirical and is highly variable among providers. Our objective in this study was to test the hypothesis that infant pulmonary function testing (iPFT) would reveal distinct phenotypes in patients with established sBPD during the initial NICU stay. METHODS: A prospective cohort study with data prospectively collected on infants with sBPD from May 1, 2003, to June 30, 2016. iPFT data were used to classify the patients as obstructive, restrictive, or mixed. RESULTS: The median gestational age at birth was 25 weeks (interquartile range [IQR], 24-27 weeks) and the median birth weight was 707 g (IQR, 581-925 g). At the time of iPFT, the median postmenstrual age was 52 weeks (IQR, 45-63 weeks), and the median weight was 4.4 kg (IQR, 3.7-6.0 kg). There were 56 (51%) patients with obstructive, 44 (40%) with mixed, and 10 (9%) with restrictive phenotypes. Moderate or severe obstruction was seen in 86% of the obstructive group and 78% of the mixed group. Of the restrictive patients, 70% had moderate and 30% had mild restriction. Bronchodilator response was seen in 74% of obstructive, 63% of mixed, and 25% of restrictive patients. CONCLUSIONS: Our findings reveal that sBPD as it is currently defined includes distinct phenotypes. Future researchers of diagnostic approaches to this population should consider the development of bedside tests to define phenotypes, and researchers in future therapeutic trials should consider the use of pulmonary function phenotyping in patient recruitment.

Static hyperinflation is associated with ventilatory limitation and exercise tolerance in adult cystic fibrosis.

INTRODUCTION: Lung hyperinflation is a potential mechanism limiting exercise tolerance. However, available data on the impact of static hyperinflation on exercise performance in adult cystic fibrosis are lacking. Furthermore, the relative contribution of both static and dynamic hyperinflation to exercise performance is unknown. OBJECTIVES: The aim of this study was to determine the impact of static hyperinflation on exercise tolerance and lung dynamics in adult cystic fibrosis. METHODS: Clinical data of 107 adult patients with cystic fibrosis, including pulmonary function, lung volumes and cardiopulmonary exercise from the Toronto Cystic Fibrosis database, were collected and analyzed. Patients were classified as having static hyperinflation with a residual volume to total lung capacity (RV/TLC) ratio of 30% or greater. RESULTS: Patients with static hyperinflation demonstrated a significant reduction in exercise performance [peak oxygen uptake (% predicted) 70 ± 17 vs 80 ± 17; P = .006] and were more likely to experience ventilatory limitation when exercising (Fisher's exact test P < .001). Correlation analysis showed significant relationships between measures of static hyperinflation [RV/TLC ratio (%)] and exercise performance [peak oxygen uptake (% predicted); r = -.38, P < .001] and dynamic hyperinflation (r = -.35, P < .001). Multiple linear regression showed that the contribution of static hyperinflation to exercise performance [peak oxygen uptake (% predicted)] was greater than that of airway obstruction (forced expiratory volume in 1 second). CONCLUSION: Clinicians working with this patient group in a pulmonary rehabilitation or health care setting may wish to consider using measures of static hyperinflation as end points to determine program or treatment efficacy.

Effect of total lung capacity, gender and height on CT airway measurements.

OBJECTIVE: Testing the hypothesis that CT airway measurements could be influenced by total lung capacity (TLC), gender and height in normal individuals. METHODS: In this ethics committee-approved prospective trial, 87 healthy never-smoking volunteers who provided written informed consent were included. From a helical CT scan of the chest, the wall thickness (WT) and the lumen area were twice measured in the third- and fourth-generation airways by three readers using a dedicated software. In addition, the TLC was also measured using CT (TLCCT). The percentage of airway area occupied by the wall (WA%) and the square root of wall area at an internal perimeter of 10 mm (√WAPi10) were calculated. CT airway measurements were compared between genders by using a mixed linear model. The correlations between height, TLCCT and CT airway measurements were tested by using a Pearson correlation analysis. These correlations were arbitrarily considered as significant if there was a significant correlation observed for each of the six measurement sessions. RESULTS: √WAPi10, WT3rd and WT4th were significantly different between genders. For both genders, there was no significant correlation between any airway measurements and TLCCT. In females only, WT3rd and WT4th were significantly and negatively correlated with height. CONCLUSION: √WAPi10, WT3rd and WT4th are different in males and females. WT3rd and WT4th are correlated with height in females only but not with TLC or in males. Advances in knowledge: CT airway measurements are influenced by gender and by height in females only but not by TLC. They should be adjusted according to gender and height in females.

Comparison of plethysmographic and helium dilution lung volumes in patients with a giant emphysematous bulla as selection criteria for endobronchial valve implant.

OBJECTIVES: To assess whether the difference in lung volume measured with plethysmography and with the helium dilution technique could differentiate an open from a closed bulla in patients with a giant emphysematous bulla and could be used as a selection criterion for the positioning of an endobronchial valve. METHODS: We reviewed the data of 27 consecutive patients with a giant emphysematous bulla undergoing treatment with an endobronchial valve. In addition to standard functional and radiological examinations, total lung capacity and residual volume were measured with the plethysmographic and helium dilution technique. We divided the patients into 2 groups, the collapse or the no-collapse group, depending on whether the bulla collapsed or not after the valves were put in position. We statistically evaluated the intergroup differences in lung volume and outcome. RESULTS: In the no-collapse group (n = 6), the baseline plethysmographic values were significantly higher than the helium dilution volumes, including total lung capacity (188 ± 14 vs 145 ± 13, P = 0.0007) and residual volume (156 ± 156 vs 115 ± 15, P = 0.001). In the collapse group, there was no significant difference in lung volumes measured with the 2 methods. A difference in total lung capacity of ≤ 13% and in residual volume of ≤ 25% measured with the 2 methods predicted the collapse of the bulla with a success rate of 83% and 84%, respectively. Only the collapse group showed significant improvement in functional data. CONCLUSIONS: Similar values in lung volumes measured with the 2 methods support the hypothesis that the bulla communicates with the airway (open bulla) and thus is likely to collapse when the endobronchial valve is implanted. Further studies are needed to validate our model.

Lung volumes and airway resistance in patients with a possible restrictive pattern on spirometry / Volumes pulmonares e resistência das vias aéreas em pacientes com possível padrão restritivo à espirometria

ABSTRACT Objective: Many patients with proportional reductions in FVC and FEV1 on spirometry show no reduction in TLC. The aim of this study was to evaluate the role that measuring lung volumes and airway resistance plays in the correct classification of patients with a possible restrictive pattern on spirometry. Methods: This was a prospective study involving adults with reduced FVC and FEV1, as well as an FEV1/FV(C) ratio within the predicted range. Restrictive lung disease (RLD) was characterized by TLC below the 5th percentile, as determined by plethysmography. Obstructive lung disease (OLD) was characterized by high specific airway resistance, significant changes in post-bronchodilator FEV1, or an FEF25-75% < 50% of predicted, together with a high RV/TLC ratio. Nonspecific lung disease (NLD) was characterized by TLC within the predicted range and no obstruction. Combined lung disease (CLD) was characterized by reduced TLC and findings indicative of airflow obstruction. Clinical diagnoses were based on clinical suspicion, a respiratory questionnaire, and the review of tests of interest. Results: We included 300 patients in the study, of whom 108 (36%) were diagnosed with RLD. In addition, 120 (40%) and 72 (24%) were diagnosed with OLD/CLD and NLD, respectively. Among the latter, 24 (33%) were clinically diagnosed with OLD. In this sample, 151 patients (50.3%) were obese, and obesity was associated with all patterns of lung disease. Conclusions: Measuring lung volumes and airway resistance is often necessary in order to provide an appropriate characterization of the pattern of lung disease in patients presenting with a spirometry pattern suggestive of restriction. Airflow obstruction is common in such cases.

RESUMO Objetivo: Muitos pacientes com redução proporcional de CVF e VEF1 na espirometria não têm CPT reduzida. O objetivo deste estudo foi avaliar o papel da medida dos volumes pulmonares e da resistência das vias aéreas para a classificação correta de pacientes com possível restrição à espirometria. Métodos: Estudo prospectivo de adultos com CVF e VEF1 reduzidos e relação VEF1/CV(F) na faixa prevista. Distúrbio ventilatório restritivo (DVR) foi definido por CPT < 5º percentil por pletismografia. Distúrbio ventilatório obstrutivo (DVO) foi caracterizado por resistência específica de vias aéreas elevada, resposta significativa do VEF1 pós-broncodilatador e/ou um FEF25-75% < 50% do previsto associado a uma relação VR/CPT elevada. Distúrbio ventilatório inespecífico (DVI) foi caracterizado por CPT na faixa prevista e ausência de obstrução. Distúrbio ventilatório combinado (DVC) foi caracterizado por CPT reduzida e achados indicativos de obstrução ao fluxo aéreo. Os diagnósticos clínicos foram baseados em suspeita clínica, um questionário respiratório e revisão de exames de interesse. Resultados: Foram incluídos 300 pacientes no estudo, dos quais 108 (36%) tiveram diagnóstico de DVR, enquanto 120 (40%) foram diagnosticados com DVO ou DVC e 72 (24%) com DVI. Destes últimos, 24 (33%) tinham diagnóstico clínico de DVO. Nesta amostra, 151 pacientes (50,3%) eram obesos, e isso se associou com todos os padrões de distúrbios funcionais. Conclusões: Medidas dos volumes pulmonares e da resistência das vias aéreas são frequentemente necessárias para a caracterização adequada do tipo de distúrbio funcional em casos com possível restrição à espirometria. A obstrução ao fluxo aéreo é comum nesses casos.

Low-dose computed tomography volumetry for subtyping chronic lung allograft dysfunction.

BACKGROUND: The long-term success of lung transplantation is challenged by the development of chronic lung allograft dysfunction (CLAD) and its distinct subtypes of bronchiolitis obliterans syndrome (BOS) and restrictive allograft syndrome (RAS). However, the current diagnostic criteria for CLAD subtypes rely on total lung capacity (TLC), which is not always measured during routine post-transplant assessment. Our aim was to investigate the utility of low-dose 3-dimensional computed tomography (CT) lung volumetry for differentiating RAS from BOS. METHODS: This study was a retrospective evaluation of 63 patients who had developed CLAD after bilateral lung or heart‒lung transplantation between 2006 and 2011, including 44 BOS and 19 RAS cases. Median post-transplant follow-up was 65 months in BOS and 27 months in RAS. The median interval between baseline and the disease-onset time-point for CT volumetry was 11 months in both BOS and RAS. Chronologic changes and diagnostic accuracy of CT lung volume (measured as percent of baseline) were investigated. RESULTS: RAS showed a significant decrease in CT lung volume at disease onset compared with baseline (mean 3,916 ml vs 3,055 ml when excluding opacities, p < 0.0001), whereas BOS showed no significant post-transplant change (mean 4,318 ml vs 4,396 ml, p = 0.214). The area under the receiver operating characteristic curve of CT lung volume for differentiating RAS from BOS was 0.959 (95% confidence interval 0.912 to 1.01, p < 0.0001) and the calculated accuracy was 0.938 at a threshold of 85%. CONCLUSION: In bilateral lung or heart‒lung transplant patients with CLAD, low-dose CT volumetry is a useful tool to differentiate patients who develop RAS from those who develop BOS.

Association of pulse wave velocity with total lung capacity: A cross-sectional analysis of the BOLD London study.

BACKGROUND: Low lung function, measured using spirometry, has been associated with mortality from cardiovascular disease, but whether this is explained by airflow obstruction or restriction is a question that remains unanswered. OBJECTIVES: To assess the association of total lung capacity (TLC), forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) with several cardio-metabolic and inflammatory markers. METHODS: In the follow up of the Burden of Lung Disease (BOLD) study in London, acceptable post-bronchodilator spirometric, pulse rate, pulse wave velocity and blood pressure data were obtained from 108 participants. Blood samples for measurement of cardio-metabolic and inflammatory markers were also collected from these participants. Association of lung function and volume with the different biomarkers was examined in multivariable linear regression models adjusted for potential confounders. RESULTS: Following adjustment for age, sex, height, and ethnicity, TLC (adjusted coefficient = -1.53; 95% CI: -2.57, -0.49) and FVC (adjusted coefficient = -2.66; 95% CI: -4.98, -0.34) were inversely associated with pulse wave velocity, and further adjustment for smoking status, pack-years and body mass index (BMI) did not materially change these results. FEV1 was inversely associated with systolic blood pressure, and adjustment for smoking status, pack-years and BMI made this association stronger (adjusted coefficient = -9.47; 95% CI: -15.62, -3.32). CONCLUSION: The inverse association of pulse wave velocity, which is a marker of cardiovascular disease, with TLC suggests that the association of the former with low FVC is independent of airflow obstruction. The association between FEV1 with systolic blood pressure after adjustment for FVC suggests an association with airflow obstruction rather than with restricted spirometry.

Intravenous antibiotics for pulmonary exacerbations in people with cystic fibrosis.

BACKGROUND: Cystic fibrosis is a multi-system disease characterised by the production of thick secretions causing recurrent pulmonary infection, often with unusual bacteria. Intravenous antibiotics are commonly used in the treatment of acute deteriorations in symptoms (pulmonary exacerbations); however, recently the assumption that exacerbations are due to increases in bacterial burden has been questioned. OBJECTIVES: To establish if intravenous antibiotics for the treatment of pulmonary exacerbations in people with cystic fibrosis improve short- and long-term clinical outcomes. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the reference lists of relevant articles and reviews and ongoing trials registers.Date of last search of Cochrane trials register: 27 July 2015. SELECTION CRITERIA: Randomised controlled trials and the first treatment cycle of cross-over studies comparing intravenous antibiotics (given alone or in an antibiotic combination) with placebo, inhaled or oral antibiotics for people with cystic fibrosis experiencing a pulmonary exacerbation. DATA COLLECTION AND ANALYSIS: The authors assessed studies for eligibility and risk of bias and extracted data. MAIN RESULTS: We included 40 studies involving 1717 participants. The quality of the included studies was largely poor and, with a few exceptions, these comprised of mainly small, inadequately reported studies.When comparing treatment with a single antibiotic to a combined antibiotic regimen, those participants receiving a combination of antibiotics experienced a greater improvement in lung function when considered as a whole group across a number of different measurements of lung function, but with very low quality evidence. When limited to the four placebo-controlled studies (n = 214), no difference was observed, again with very low quality evidence. With regard to the review's remaining primary outcomes, there was no effect upon time to next exacerbation and no studies in any comparison reported on quality of life. There were no effects on the secondary outcomes weight or adverse effects. When comparing specific antibiotic combinations there were no significant differences between groups on any measure. In the comparisons between intravenous and nebulised antibiotic or oral antibiotic (low quality evidence), there were no significant differences between groups on any measure. No studies in any comparison reported on quality of life. AUTHORS' CONCLUSIONS: The quality of evidence comparing intravenous antibiotics with placebo is poor. No specific antibiotic combination can be considered to be superior to any other, and neither is there evidence showing that the intravenous route is superior to the inhaled or oral routes. There remains a need to understand host-bacteria interactions and in particular to understand why many people fail to fully respond to treatment.