COPD diagnosis related to different guidelines and spirometry techniques

Background

Several studies have indicated that one of the most potent mediators involved in pulmonary vascular remodeling is vascular endothelial growth factor (VEGF). This study was designed to determine whether airway VEGF level reflects pulmonary vascular remodeling in patients with bronchitis-type of COPD.

Methods

VEGF levels in induced sputum were examined in 23 control subjects (12 non-smokers and 11 ex-smokers) and 29 patients with bronchitis-type of COPD. All bronchitis-type patients performed exercise testing with right heart catheterization.

Results

The mean pulmonary arterial pressure (mPAP) and pulmonary vascular resistance (PVR) after exercise were markedly increased in all bronchitis-type patients. However, both parameters after exercise with breathing of oxygen was significantly lower than in those with breathing of room air. To attenuate the effect of hypoxia-induced pulmonary vasoconstriction during exercise, we used the change in mPAP or PVR during exercise with breathing of oxygen as a parameter of pulmonary vascular remodeling. Change in mPAP was significantly correlated with VEGF level in induced sputum from patients with chronic bronchitis (r = 0.73, p = 0.0001). Moreover, change in PVR was also correlated with VEGF level in those patients (r = 0.57, p = 0.003).

Conclusion

A close correlation between magnitude of pulmonary hypertension with exercise and VEGF level in bronchitis-type patients could be observed. Therefore, these findings suggest the possibility that VEGF level in induced sputum is a non-invasive marker of pulmonary vascular remodeling in patients with bronchitis-type of COPD.     

Methacholine versus histamine: paradoxical response of spirometry and ventilation distribution.

We investigated the differential effect of histamine and methacholine on spirometry and ventilation distribution (where indexes S(cond) and S(acin) represent conductive and acinar ventilation heterogeneity; Verbanck S, Schuermans D, Van Muylem A, Noppen M, Paiva M, and Vincken W. J Appl Physiol 83: 1807-1816, 1997). Thirty normal subjects were challenged with cumulative doses of 6.52 micromol histamine and, on a separate day, with either 6.67 micromol methacholine (equal-dose group; n = 15) or 13.3 micromol methacholine (double-dose group; n = 15). Largest average forced expiratory volume in 1 s (FEV(1)) decreases or S(cond) increases obtained in either group were -9% and +286%, respectively; S(acin) remained unaffected at all times. In the equal-dose group, a smaller FEV(1) decline (P = 0.002) after methacholine was paralleled by a smaller S(cond) increase (P = 0.041) than with histamine. However, in the double-dose group, methacholine maintained a smaller FEV(1) decline (P = 0.009) while inducing a larger S(cond) increase (P = 0.006) than did histamine. The differential action of histamine and methacholine is confined to the conductive airways, where histamine likely causes the greatest overall airway narrowing and methacholine induces the largest parallel heterogeneity in airway narrowing, probably at the level of the large and small conductive airways, respectively. The observed ventilation heterogeneities predict a risk for dissociation between ventilation-perfusion mismatch and spirometry, particularly after methacholine challenge.     

Exercise-induced bronchoconstriction alters airway nitric oxide exchange in a pattern distinct from spirometry

Exhaled nitric oxide (NO) is altered in asthmatic subjects with exercise-induced bronchoconstriction (EIB). However, the physiological interpretation of exhaled NO is limited because of its dependence on exhalation flow and the inability to distinguish completely proximal (large airway) from peripheral (small airway and alveolar) contributions. We estimated flow-independent NO exchange parameters that partition exhaled NO into proximal and peripheral contributions at baseline, postexercise challenge, and postbronchodilator administration in steroid-naive mild-intermittent asthmatic subjects with EIB (24-43 yr old, n = 9) and healthy controls (20-31 yr old, n = 9). The mean +/- SD maximum airway wall flux and airway diffusing capacity were elevated and forced expiratory flow, midexpiratory phase (FEF(25-75)), forced expiratory volume in 1 s (FEV(1)), and FEV(1)/forced vital capacity (FVC) were reduced at baseline in subjects with EIB compared with healthy controls, whereas the steady-state alveolar concentration of NO and FVC were not different. Compared with the response of healthy controls, exercise challenge significantly reduced FEV(1) (-23 +/- 15%), FEF(25-75) (-37 +/- 18%), FVC (-12 +/- 12%), FEV(1)/FVC (-13 +/- 8%), and maximum airway wall flux (-35 +/- 11%) relative to baseline in subjects with EIB, whereas bronchodilator administration only increased FEV(1) (+20 +/- 21%), FEF(25-75) (+56 +/- 41%), and FEV(1)/FVC (+13 +/- 9%). We conclude that mild-intermittent steroid-naive asthmatic subjects with EIB have altered airway NO exchange dynamics at baseline and after exercise challenge but that these changes occur by distinct mechanisms and are not correlated with alterations in spirometry.     

Acoustic and spirometry parameters of forced expiratory sounds during a five-day dry immersion

The dynamic studies of the parameters of forced expiration under the conditions of a five-day dry immersion involved seven healthy male subjects aged 20 to 25 years. During forced expiration, spirometry tests were performed simultaneously with tracheal sounds being recorded by a microphone. A number of parameters, including the acoustic duration of the forced-expiration tracheal sounds, the lungs’ forced vital capacity, the 1-s forced expiration volume, the peak expiratory flow, and time of achieving the peak expiratory flow, were recorded before dry immersion, on days 1 and 4 of immersion, and the next day after the termination of immersion. There was a significant decrease (by 8.4%) in the peak expiratory flow on day 1 of immersion; however, by day 4 of immersion, the peak expiratory flow increased by 8.9%, reaching its baseline values. The lungs’ forced vital capacity and the forced expiration volume during 1 second, on the average, did not change throughout the experiment. There was a significant increase (by 17%) in the duration of the forced expiration tracheal sounds after the immersion, which suggests an increase in respiratory resistance and needs further studies. A moderate negative correlation between the duration of the forced expiration tracheal sounds and Gensler’s index (r = ?0.63) was found, whereas the correlation with other spirometry parameters was weak or absent.     

Epidemiology,genetics, and subtyping of preserved ratio impaired spirometry (PRISm) in COPDGene

Background

Preserved Ratio Impaired Spirometry (PRISm), defined as a reduced FEV₁ in the setting of a preserved FEV₁/FVC ratio, is highly prevalent and is associated with increased respiratory symptoms, systemic inflammation, and mortality. Studies investigating quantitative chest tomographic features, genetic associations, and subtypes in PRISm subjects have not been reported.

Methods

Data from current and former smokers enrolled in COPDGene (n = 10,192), an observational, cross-sectional study which recruited subjects aged 45–80 with ≥10 pack years of smoking, were analyzed. To identify epidemiological and radiographic predictors of PRISm, we performed univariate and multivariate analyses comparing PRISm subjects both to control subjects with normal spirometry and to subjects with COPD. To investigate common genetic predictors of PRISm, we performed a genome-wide association study (GWAS). To explore potential subgroups within PRISm, we performed unsupervised k-means clustering.

Results

The prevalence of PRISm in COPDGene is 12.3%. Increased dyspnea, reduced 6-minute walk distance, increased percent emphysema and decreased total lung capacity, as well as increased segmental bronchial wall area percentage were significant predictors (p-value <0.05) of PRISm status when compared to control subjects in multivariate models. Although no common genetic variants were identified on GWAS testing, a significant association with Klinefelter’s syndrome (47XXY) was observed (p-value < 0.001). Subgroups identified through k-means clustering include a putative “COPD-subtype”, “Restrictive-subtype”, and a highly symptomatic “Metabolic-subtype”.

Conclusions

PRISm subjects are clinically and genetically heterogeneous. Future investigations into the pathophysiological mechanisms behind and potential treatment options for subgroups within PRISm are warranted.

Trial registration

Clinicaltrials.gov Identifier: NCT000608764.

Electronic supplementary material

The online version of this article (doi:10.1186/s12931-014-0089-y) contains supplementary material, which is available to authorized users.     

Analysis of diaphragm movement during tidal breathing and during its activation while breath holding using MRI synchronized with spirometry

Using magnetic resonance imaging (MRI) in conjunction with synchronized spirometry we analyzed and compared diaphragm movement during tidal breathing and voluntary movement of the diaphragm while breath holding. Breathing cycles of 16 healthy subjects were examined using a dynamic sequence (77 slices in sagittal plane during 20 s, 1NSA, 240x256, TR4.48, TE2.24, FA90, TSE1, FOV 328). The amplitude of movement of the apex and dorsal costophrenic angle of the diaphragm were measured for two test conditions: tidal breathing and voluntary breath holding. The maximal inferior and superior positions of the diaphragm were subtracted from the corresponding positions during voluntary movements while breath holding. The average amplitude of inferio-superior movement of the diaphragm apex during tidal breathing was 27.3+/-10.2 mm (mean +/- SD), and during voluntary movement while breath holding was 32.5+/-16.2 mm. Movement of the costophrenic angle was 39+/-17.6 mm during tidal breathing and 45.5+/-21.2 mm during voluntary movement while breath holding. The inferior position of the diaphragm was lower in 11 of 16 subjects (68.75 %) and identical in 2 of 16 (12.5 %) subjects during voluntary movement compared to the breath holding. Pearson's correlation coefficient was used to demonstrate that movement of the costophrenic angle and apex of the diaphragm had a linear relationship in both examined situations (r=0.876). A correlation was found between the amplitude of diaphragm movement during tidal breathing and lung volume (r=0.876). The amplitude of movement of the diaphragm with or without breathing showed no correlation to each other (r=0.074). The movement during tidal breathing shows a correlation with the changes in lung volumes. Dynamic MRI demonstrated that individuals are capable of moving their diaphragm voluntarily, but the amplitude of movement differs from person to person. In this study, the movements of the diaphragm apex and the costophrenic angle were synchronous during voluntary movement of the diaphragm while breath holding. Although the sample is small, this study confirms that the function of the diaphragm is not only respiratory but also postural and can be voluntarily controlled.     

Influence of forward leaning and incentive spirometry on inspired volumes and inspiratory electromyographic activity during breathing exercises in healthy subjects

Breathing exercises (BE), incentive spirometry and positioning are considered treatment modalities to achieve lung re-expansion. This study evaluated the influence of incentive spirometry and forward leaning on inspired tidal volumes (V_T) and electromyographic activity of inspiratory muscles during BE. Four modalities of exercises were investigated: deep breathing, spirometry using both flow and volume-oriented devices, and volume-oriented spirometry after modified verbal instruction. Twelve healthy subjects aged 22.7 ± 2.1 years were studied. Surface electromyography activity of diaphragm, external intercostals, sternocleidomastoid and scalenes was recorded. Comparisons among the three types of exercises, without considering spirometry after modified instruction, showed that electromyographic activity and V_T were lower during volume-oriented spirometry (p = 0.000, p = 0.054, respectively). Forward leaning resulted in a lower V_T when compared to upright sitting (p = 0.000), but electromyographic activity was not different (p = 0.606). Inspired V_T and electromyographic activity were higher during volume-oriented spirometry performed after modified instruction when compared with the flow-oriented device (p = 0.027, p = 0.052, respectively). In conclusion BE using volume-oriented spirometry before modified instruction resulted in a lower work of breathing as a result of a lower V_T and was not a consequence of the device type used. Forward leaning might not be assumed by healthy subjects during situations of augmented respiratory demand.     

Effect of 16 weeks diving practice at two different times of day on the pulmonary function,spirometry measurements and 6-minute walk test data of healthy professional Tunisian scuba divers

The aim of this study was to investigate the effect of time of the day (TOD) and 16 weeks diving practice (16WDP) on the spirometric parameters and 6-min walk test data (6MWT) on professional Tunisian scuba divers. In randomized order, 36 health males divided into 3 groups [morning practice group) (MPG): n = 12; evening practice group (EPG): n = 12; control group (CG) n = 12] participated voluntary in this study. They performed spirometry measurements and 6MWT during two periods: [before-season (June 05–10), and after-season (October 05–10)]. Our results revealed that assessment sessions comprised the following: FVC, FEV1, FEV1/FVC and PEF. Results were analyzed by applying repeated measures analysis of variance ANOVA. The spirometric parameters were similar upon two times of day on both EPG and MPG before the season (i.e. FEV1, FVC). Likewise, our finding revealed a significant decrease in lung functions following the 16 weeks practice of scuba diving upon two times of day. Thus, this period of hyperbaric scuba diving practice lead a significant alteration of lung function parameters with decrease of percent of variation in EPG vs. CEG compared to MPG vs. CMG: (i.e. FEV1, FVC, and PEF). In conclusion, 16 weeks of hyperbaric scuba diving lead a significant change in the spirometric and 6MWT values and respiratory problem with damage on lung function in healthy adult divers older than 40 years. Professional divers are recommended to have practice diving in the morning.