Small airway function in acromegaly

Small airway function was studied in 21 acromegalic patients (13 females, 8 males) and quantitated as the maximal expiratory flow at 25 and 50% of vital capacity (VEmax25, VEmax50) breathing room air, as the difference of flow at 50% of VC breathing air and 80% helium 20% O2 (delta Vmax50) and as the volume of equal flows (VisoV). In addition, lung volumes were investigated by spirometry and body plethysmography. Static lung volumes were statistically significantly increased in both male and female acromegalic patients (p less than 0.05), but RV/TLC and FEV1/FVC did not change (p greater than 0.1). VEmax25, delta Vmax50 and VisoV showed an abnormal function of small airways in nonsmoking acromegalic patients. However, smoking acromegalics did not differ significantly from 'normal' smoking subjects, suggesting that the dysfunction of small airways is not a contributory factor to mortality from the disease. Maximal expiratory flows, when related to lung volume, were reduced in acromegalic women. Abnormal small airway function in acromegaly could either be due to obstruction or, more likely, to an exaggeration of dysanaptic lung growth.     

Exaled nitric oxide and air trapping correlation in asthmatic children

Exhaled nitric oxide (eNO) levels have been shown to correlate with atopy and with airway hyperresponsiveness but not with standard spirometry. The aim of our study was to evaluate the correlation between eNo levels and functional residual capacity (FRC), residual volume (RV), RV to total lung capacity (TLC) ratio, and pulmonary resistances in asthmatic children ages 6-13 years. Forty-nine patients (35 males) were enrolled in the study. Nineteen of them were not receiving inhaled corticosteroids. The eNO levels were measured by chemiluminescence's analyzer and lung function study were performed by body box plethysmography. As expected, there was no correlation between eNO levels and forced vital capacity (FVC); forced expiratory volume in the first second (FEV1); mid respiratory flow between 25 and 75% of the vital capacity (MEF(25 -75)), FEV1/FVC, and pulmonary resistances. Instead a correlation was found between eNO level and RV both considering all the study population together (r = 0.51, P = 0.001) and separately the asthmatic children not receiving ICS (r = 0.6, P = 0.003). In the patients receiving ICS the correlation was still present (r = 0.43, P = 0.01). The correlation between eNo levels and RV may reflect the effect of airway inflammation on NO production and diffusion as well as peripheral airway trapping and consequent RV.     

Airway distensibility with lung inflation after allogeneic haematopoietic stem-cell transplantation

The ability to reverse induced-bronchoconstriction by deep-inhalation increases after allogeneic haematopoietic stem-cell transplantation (HSCT), despite a decreased total lung capacity (TLC). We hypothesized that this effect may be due to an increased airway distensibility with lung inflation, likely related to an increment in lung stiffness. We studied 28 subjects, 2 weeks before and 2 months after HSCT. Within-breath respiratory system conductance (G(rs)) at 5, 11 and 19Hz was measured by forced oscillation technique (FOT) at functional residual capacity (FRC) and TLC. Changes in conductance at 5Hz (G(rs5)) were related to changes in lung volume (ΔG(rs5)/ΔV(L)) to estimate airway distensibility. G(rs) at FRC showed a slight but significant increase at all forcing frequencies by approximately 12-16%. TLC decreased after HSCT whereas the ΔG(rs5)/ΔV(L) ratio became higher after than before HSCT and was positively correlated (R(2)=0.87) with lung tissue density determined by quantitative CT scanning. We conclude that airway caliber and distensibility with lung inflation are increased after HSCT. This effect seems to be related to an increase in lung stiffness and must be taken into account when interpreting lung function changes after HSCT.     

Measurement of Lung Volumes

Lung volume measurements always determine total lung capacity (TLC), and most measurement techniques also determine functional residual capacity (FRC) and residual volume (RV). These measurements are needed less often than spirometry-derived values and require somewhat more difficult methods than required by spirometry. As with spirometry, accurate interpretation relies on appropriate reference values, standardized methodology and technically well-performed testing. A reduction in TLC defines chest restriction. Increases in TLC, FRC and RV are often seen in patients with airway obstruction. Patients with mixed restrictive and obstructive disease may have spirometry results that are difficult to interpret, and it is in these patients that lung volume measurements may be especially helpful.     

Localized morphometric deformations of small airways and alveoli in intact mouse lungs under quasi-static inflation

Localized morphometric deformations of small airways and alveoli during respiration have several biomechanical and physiological implications. We developed fast synchrotron radiation CT system to visualize the small airways and alveoli of an intact mouse lung without fixation and dehydration, and analyzed their localized morphometric deformations between functional residual capacity (FRC) and total lung capacity (TLC). The maximum resolution of 32.6lp/mm at the 5% modulation transfer function level can be achieved with 11.8-microm voxels and 7-min scanning. Compared with the values at FRC, the diameter and length for smaller airways (diameter at FRC <200 microm) increased by 68.8% and 29.5% (averaged value), and those for larger airways (diameter at FRC >400 microm) increased by 45.2 and 22.9% (averaged value), at TLC. Moreover we defined the volume behavior as the percentage of airway volume at FRC for TLC. The volume behavior for the small airways was not similar to that of the lung volume. These results indicated that all airways did not behave homogenously.     

Reference values and modelling of lung function development as a transcendent function of age, body height and mass

We present new lung function reference values based on an investigation of 1024 healthy subjects aged 6-81 years. The dependent variables, i.e. VC, FEV1, RV, FRC, TLC, PEF, MEF50 and MEF25 are expressed as transcendent functions of age, body height and mass. A single equation covers the age range from 6 to 81 years and reflects certain phenomena such as growth, maturation, ageing, sex differences and the undermass-overmass effect. This allows a more accurate determination of individualized reference values and normal limits.     

Evoked corticospinal output to the human scalene muscles is altered by lung volume

Increases in lung volume inhibit the inspiratory output from the medulla, but the effect of lung inflation on the voluntary control of breathing in humans is not known. We tested corticospinal excitability using transcranial magnetic stimulation (TMS) to evoke a response in the scalene muscles. TMS was delivered at rest at three different lung volumes between functional residual capacity (FRC) and total lung capacity (TLC) during incremental inspiratory and incremental expiratory manoeuvres. Motor evoked potentials (MEPs) in scalenes were ～50% larger at a high lung volume (FRC+～90% inspiratory capacity [IC]) compared to lower lung volumes (FRC and FRC+～40% IC) in both inspiratory and expiratory manoeuvres (p<0.001). The change in MEP size was not due to differences in pre-stimulus EMG amplitude (p=0.29). The results suggest a differential effect of lung inflation on the automatic and voluntary control of breathing in humans.     

Total lung capacity in Andean highlanders

Total lung capacity (TLC), residual volume (RV), and vital capacity (VC), as well as related measures of pulmonary function, were assessed in a sample of 39 male and 23 female native highlanders of Aymara ancestry (20.1–28.8 years) who were residing in La Paz, Bolivia (average altitude of about 3,600 m). After controlling for body and chest size, most measures of respiratory function were significantly larger in males than females (P < .05). Absolute TLC (1 BTPS) was significantly larger in the La Paz Aymara males than in highland Peruvian or Tibetan males (P < .05) but, after controlling for body size, TLC was only 1 and 4% larger in the La Paz Aymara than in highland Peruvians or Tibetans, respectively. Also, comparison of the body size-adjusted percentage increases in TLC, VC and RV above U.S. sea-level reference values in selected highland populations indicated that the enhanced TLCs of highlanders are primarily due to an enhancement of RV and secondarily due to an enhancement of VC. © 1994 Wiley-Liss, Inc.     

Effect of lung volume reduction surgery for emphysema on diaphragm function

Preoperative prediction of a successful outcome following lung volume reduction surgery (LVRS) for emphysema is imperfect. One mechanism could be improvement in respiratory muscle function yet controversy exists regarding the magnitude and mechanism of such an improvement. Therefore, we measured diaphragm strength in 18 patients before and after LVRS. Mean (S.D.) FRC fell from 6.53 to 5.40 l (p = 0.0001). Mean sniff transdiaphragmatic pressure increased from 76 to 87 cm H2O (14%, p < 0.03) and mean twitch transdiaphragmatic pressure (Tw Pdi) increased by 2.5 cm H2O at 3 months (12%, p = 0.03). There was a highly significant increase in twitch esophageal pressure (Tw Pes) (60%, p < 0.0001), which was maintained at 12 months (46% increase, p = 0.0004). No change was observed in quadriceps twitch tension in nine subjects in whom it was measured. After LVRS the ratio Tw Pes:Tw Pdi increased from 0.24 to 0.37 at 3 months (p = 0.0003) and 0.36 at 12 months (p = 008). Low values of Sn Pdi, Sn Pes, Tw Pes and a high RV/TLC ratio were the preoperative variables most predictive of improvement in shuttle walking distance. We conclude that LVRS improves diaphragm function primarily by alteration of lung volume. Patients with poor diaphragm function and high RV/TLC ratio preoperatively are most likely to benefit from the procedure.     

Bronchoconstriction induced by spirometric maneuvers in patients with bronchial asthma

We analyzed forced expiration maneuver-induced bronchoconstriction in 14 asthmatic patients and in seven normal subjects by breaking down the forced expiration maneuver of spirometry (the FVC maneuver) into two phases: a slow, deep inspiration to the total lung capacity (TLC) (the DI maneuver) and a forced expiration to the residual volume (RV) (the PFV maneuver). Specific airway conductance (sGaw) was measured at functional residual capacity (FRC) after each of the three maneuvers. All of the maneuvers caused the greatest bronchoconstriction immediately after completion of the maneuver. The mean decreases in the sGaw immediately after the FVC, DI, and PFV maneuvers were 45.0 +/- 6.6 (SD)% (P less than .001), 29.6 +/- 5.3% (P less than .001), and 16.7 +/- 5.3% (P less than .03), respectively. The decrease in sGaw by the FVC maneuver was very close to the combined algebraic sum of the DI maneuver and the PFV maneuver. The normal subjects did not show any changes in the sGaw by any of the maneuvers. The inhalation of albuterol almost abolished the response of bronchoconstriction to any of the three maneuvers, but inhalation of an anticholinergic agent, ipratropium bromide, did blunt the response. This study suggests that forced expiration maneuver-induced bronchoconstriction in asthmatics can be caused not only by deep inspiration to the TLC but also by forced expiration to the RV, and that the bronchoconstriction may be brought about mainly by an increase in parasympathetic activity.     

Effect of a deep inspiration on expiratory flow in normals and patients with chronic obstructive pulmonary disease

Normal control subjects and individuals with chronic obstructive pulmonary disease (COPD) were studied by measuring routine lung function tests as well as maximal (MEFV) and partial expiratory flow-volume (PEFV) curves and lung elastic recoil (Pst,L) before and after a total lung capacity (TLC) volume history. In the normal subjects: before bronchodilators airflow increased significantly, whereas Pst,L and upstream segment resistance (Rus) decreased significantly following inspiration to TLC; after administration of inhaled bronchodilators, flow rates were higher on the PEFV than on MEFV curves; nevertheless, because Pst,L decreased substantially following a deep breath, post-bronchodilator Rus was still somewhat reduced by deep inspiration. In the subjects with COPD flow rates on PEFV curves were as high or exceeded flow rates on MEFV curves in 76/100 studies; the ratio of flow rates (PEFV)/flow rates (MEFV) increased as pulmonary function worsened; as in normal subjects, Pst,L diminished in COPD subjects following deep inspiration; although flow rates increased on both PEFV and MEFV curves after bronchodilators, the increments in flow were considerably larger on PEFV maneuvers.     

The Bronchodilator Response of In Vivo Specific Airway Compliance in Adults with Asthma

A new technique has been developed to determine in vivo airway compliance in humans that is specific to airway size and transpulmonary pressure, and can be represented as a three-dimensional surface. As yet, the ability of this technique to detect changes in specific airway compliance with disease status has not been demonstrated. The aim of this study was to assess whether this technique could determine changes in airway compliance which are thought to occur with altered smooth muscle tone in adults with asthma. Airway compliance was measured and displayed as a surface in adults with asthma before and after a reduction in smooth muscle tone by bronchodilator administration. Compliance, with respect to airway size, was calculated at three specific lung volumes; functional residual capacity (FRC), total lung capacity (TLC), and midway between FRC and TLC (MID). After bronchodilator, airway compliance increased at FRC and MID in the smaller airways (<3?mm). Furthermore, airway compliance under both conditions was greater in the smaller airways compared to the larger airways. In conclusion, our method may have future utility in assessing changes in airway compliance in respiratory diseases such as asthma.     

Inspiratory and expiratory lung pressure-volume curve in healthy males and females

Quasistatic lung inspiratory and expiratory pressure-volume curves were obtained in 58 healthy nonsmoking males (mean age +/- SD: 42.8 +/- 15.1 years; range 22.70) and 56 healthy nonsmoking females (mean age +/- SD: 41.4 +/- 15.6 years; range: 21-76). Inspiratory and expiratory lung recoil pressures were measured at fixed percentages of TLC (100, 95, 90, 80, 70, 60 and 50%). In both sexes, inspiratory as well as expiratory lung recoil pressures were found to decrease linearly with aging (p less than 0.01 for all r values). There was no significant difference between males and females. At and above the 70% TLC level, the slopes of the age-related decreases in lung recoil were similar for the inspiratory and expiratory curves. At the 60% TLC level, the decrease in expiratory lung recoil was significantly (p less than 0.01) faster than the decrease in inspiratory lung recoil, presumably reflecting the influence of airway opening on the inspiratory pressure in older subjects. The shape of the expiratory PV curve described by the K index of the exponential model was similar in both sexes and changed with aging, K increasing significantly (p less than 0.01). By contrast, the shape of the inspiratory limb of the PV curve did not vary with aging. Consequently, the shape of the inspiratory PV curve cannot be predicted from the expiratory one and has to be measured directly.     

Influence of matching volume on reproducibility of maximal expiratory flow-volume curves

We examined the influence of "matching volume" on intrasubject variability of the descending limb of maximal expiratory flow-volume (MEFV) curves on air and helium-oxygen (He) in 18 healthy subjects and 28 patients with airflow limitation. Duplicate forced expirations were analysed according to four methods of alignment. With the first method, flows corresponding to identical percentiles of separate FVC (SEPVC) were compared. With the remaining three, we aligned curves at TLC, mid-vital capacity (VC50) and RV, respectively, for comparison of: a) flow at identical percentiles of the averaged FVC and b) expired volume at identical percentiles of the averaged peak flow. In healthy subjects, variability of flow at 50% and 75% of expired FVC (FEF50 and FEF75) did not change significantly with method, except that FEF75 on air varied more with method SEPVC than with VC50. In airflow limitation, FEF75 was significantly less reproducible when curves were matched at RV than at TLC, both on air and He. Over the latter part of expiration, an arbitrary index of variability of flow-defined volume also indicated that method RV gave the poorest precision in patients. We conclude that selection of matching volume does not influence the variability of MEFV-curves in health. In airflow limitation, however, TLC appears to be the most reliable volume for alignment.     

Pulmonary function in normal Japanese children 6 to 16 years of age

We measured pulmonary function on 182 healthy Japanese children 6 to 16 years of age living in the Tokyo area. Static lung volumes, RV/TLC (%), FRC/TLC (%), FVC, FEV1, FEV1/FVC (%), MMFR, MVV, f, VE and VO2 were measured. Multiple regression equations were obtained and the results were compared with those derived from the other equations (Kanagami (1958), Ishida (1955]. The predicted values were about 10 approximately 25% higher with our equations than those obtained from the other equations which were made more than 30 years ago. These differences were attributed to the recent improvement in growth of the Japanese children. For this reason we think it is better now to adopt new equations for the prediction of normal values in Japanese children.     

Reference values for lung function tests in females. Regression equations with smoking variables

Prediction formulas for static and dynamic spirometry, gas distribution, static lung mechanics and transfer test were derived from measurements in healthy females. The measurements included total lung capacity, residual volume, airway resistance, static elastic recoil pressure of the lung, static compliance, closing volume, slope of the alveolar plateau (phase III), flow-volume variables (including mean transit time) during breathing of air or a helium/oxygen mixture, and conventional spirometric indices. The results from 86 smokers and 100 never-smokers were evaluated separately and combined. For all lung function tests, a single regression equation including time-related smoking variables, valid for both smokers and never-smokers, was obtained. For many lung function tests, a nonlinear age coefficient resulted in a significant reduction in variance compared with simple linear models. Heavy tobacco smoking influenced most lung function tests less than ageing from 20 to 70 years, but for airway resistance, volumic airway conductance, closing volume, phase III, FEV1/VC, volume of isoflow and mean transit time the opposite was found.     

Within- and between- subject variability of indices from the closing volume and flow volume traces

The within-subject variability of consecutive measurements of indices derived from the closing volume (CV) trace and from the maximal expiratory flow volume (MEFV) curve was studied in 24 subjects. The variability of the closing volume and of the maximal expiratory flow rates at 50 percent (Vmax. 50) and 75 percent (Vmax. 75) of the expired vital capacity was about three to eight times greater than that of the FEV1, FVC or FEV1 percent. The lung volume measured from total lung capacity to the onset of airway closure (OAC) was about five times more reproducible than the CV. The coefficients of variation for the CV (as a percentage of the vital capacity), the Vmax. 75, and the OAC, both in litres and as a percentage of the vital capacity, were significantly correlated with age. No difference in the mean coefficients of variation for the CV, OAC, Vmax. 50 or Vmax. 75 were found with respect to sex, smoking habit or previous experience with the test routines. The between-subject variability of the FEV1, FVC, FEV1 percent, transfer factor, diffusion coefficient, Vmax. 50, Vmax. 75, CV and OAC was evaluated from a study of 75 asymptomatic lifetime non-smokers. The variability of the Vmax. 50, Vmax. 75 and CV was about two to eight times greater than that of the other tests used, irrespective of sex. The OAC (percent VC) was three to four times less variable than the CV. The variability of the Vmax. 50 and Vmax. 75 was reduced by, on average, 7 percent when these flow rates were expressed per litre of FVC.     

Combined pulmonary fibrosis and emphysema: How does cohabitation affect respiratory functions?

PurposeCombined pulmonary fibrosis and emphysema (CPFE) has emerged as a new syndrome with characteristics of both fibrosis and emphysema. We determined the impacts of radiologic emphysema severity on pulmonary function tests (PFTs), exercise capacity and mortality.Patients and methodsIPF patients (n = 110) diagnosed at the Chest Diseases Clinic between September 2013 and January 2016 were enrolled in the study and followed up until June 2017. Visual and digital emphysema scores, PFTs, pulmonary artery pressure (sPAP), 6-minute walking test, composite physiologic index (CPI), and survival status were recorded. Patients with emphysema and those with pure IPF were compared.ResultsThe CPFE-group had a significantly greater ratio of men(p < 0.001), lower BMI (p < 0.001), lower mean PaO₂ (p = 0.005), higher mean sPAP (p = 0.014), and higher exercise desaturation (p < 0.001). The CPFE group had a significantly higher FVC(L)(p = 0.016), and lower FEV1/FVC ratio (p = 0.002), DLCO, and DLCO/VA ratio(p = 0.03 and p = 0.005, respectively). Lung volumes of the CPFE group had significantly higher VC(p = 0.017), FRC (p < 0.001), RV(p < 0.001), RV/TLC(p < 0.001), and TLC(p < 0.001). There were significant correlations between emphysema scores and FVC (L)(p = 0.01), FEV1/FVC(p = 0.001), DLCO (p = 0.003), VC(p = 0.014), FRC (L)(p < 0.001), RV(p < 0.001), TLC(p < 0.001), and RV/TLC (p < 0.001). Mortality rates were comparable between the two groups. CPI (p = 0.02) and sPAP (p = 0.01) were independent predictors of mortality in patients with CPFE.ConclusionsThe presence and severity of emphysema affects pulmonary function in IPF. Patients with CPFE have reduced diffusion capacity, more severe air trapping, worse muscle weakness, more severe exercise desaturation, and pulmonary hypertension. CPI and pulmonary hypertension are two independent risk factors for mortality in subjects with CPFE.     

Sensitivity Analysis of Respiratory Parameter Estimates in the Constant-Phase Model

The constant-phase model is increasingly used to fit low-frequency respiratory input impedance (Zrs), highlighting the need for a better understanding of the use of the model. Of particular interest is the extent to which Zrs would be affected by changes in parameters of the model, and conversely, how reliable are parameters estimated from model fits to the measured Zrs. We performed sensitivity analysis on respiratory data from 6 adult mice, at functional residual capacity (FRC), total lung capacity (TLC), and during bronchoconstriction, obtained using a 1-25 Hz oscillatory signal. The partial derivatives of Zrs with respect to each parameter were first examined. The limits of the 95% confidence intervals, 2-dimensional pairwise and p-dimensional joint confidence regions were then calculated. It was found that airway resistance was better estimated at FRC, as determined by the confidence region limits, whereas tissue damping and elastance were better estimated at TLC. Airway inertance was poorly estimated at this frequency range, as expected. During methacholine-evoked pulmonary constriction, there was an increase in the uncertainty of airway resistance and tissue damping, but this can be compensated for by using the relative (weighted residuals) in preference over the absolute (unweighted residuals) fitting criterion. These results are consistent with experimental observation and physiological understanding.     

Lung diseases after bone marrow transplantation

Summary The case histories of 72 subsequently treated patients — 44 with acute leukemia, 10 with chronic myeloid leukemia, 16 with severe aplastic anemia and 2 with neuroblastoma — were analyzed after bone marrow transplantation (BMT) with respect to pulmonary diseases. Thirty-eight patients suffered from a total of 51 pulmonary complications, which led to death in 20. Of 13 patients, 3 died of bacterial pneumonia, all of them during granulocytopenia; 2 of 6 patients died of fungal pneumonia and 2 out of 3 of a mixed bacterialmycotic infection. Adult respiratory distress syndrome (ARDS) led to death in 2 patients. A granulocyte count under 500/µl correlated significantly (P<0.002) with the fatal outcome of bacterial, fungal and ARDS pneumonia as well as with bronchitis. Viral pneumonia led to death in 8 of 9 patients; in each there was a significant correlation (P<0.05) with graft-versus-host disease (GvHD). Patients with repeated episodes of pulmonary illness had significantly more chronic GvHD (P<0.05); several of these patients displayed a reduction in helper T cells and an increase in suppressor T cells in the peripheral blood. The natural killer (NK) cells were reduced and the percentage of activated NK cell level lay between 6% and 69%. B-cells were absent or deficient. These findings explain in part the absence of specific antibody reactivity. Five of these patients also contracted GvHD-associated obstructive bronchiolitis, which did not respond to therapy. Pulmonary infiltrates of unknown origin (including idiopathic interstitial pneumonia) occurred in 8 of the patients (11.1%), with a fatal outcome in 3 patients. Significant changes (P<0.05) in lung function after BMT appeared in the form of reduced vital capacity (VC) increased residual volume (RV) and an increase in RV expressed as the percentage of total lung capacity. Pulmonary diseases were the most common complication and cause of death in our patients after BMT.Abbreviations AEL acute erythroid leukemia - AHTCG anti-human T-cell globulin - ALL acute lymphoblastic leukemia - AML acute myeloid leukemia - ARDS adult respiratory distress syndrome - AUL acute undifferentiated leukemia - BMT bone marrow transplantation - CR complete remission - CML chronic myeloid leukemia - CMV cytomegalovirus - Ext. extensive - GvHD graft versus host disease - Lim. limited - PR partial remission - Rel. relapse - SAA severe aplastic anemia - VZV varicella zoster virus.Lung function tests - DLCO single-breath CO-diffusion capacity - FEV₁ forced expiratory volume in 1 s - KCO Krogh's constant - MBC maximal breathing capacity - RAW airway resistance - RV residual volume - SRAW specific airway resistance - TGV thoracic gas volume - TLC total lung capacity - VC vital capacity Supported in part by SFB 120, A2, B1, C1, F2