Relation of pressure and flow of pulmonary circulation in patients with chronic obstructive pulmonary disease

A series of 31 patients with various degrees of chronic obstructive pulmonary disease underwent right heart catheterization using flow-directed thermodilution catheters. Both rest and supine exercise values were obtained. The patients were divided into two groups on the basis of their reduction in forced expiratory volume in 1 s (FEV1). In patients with FEV1 values of greater than or equal to 1,300 ml (group 1), the arterial oxygen partial pressure (PaO2) did not significantly change with exercise, while in patients with FEV1 of less than or equal to 1,200 ml (group 2) PaO2 significantly (p less than 0.05) fell in response to exercise. In group 2, a significant increase of total pulmonary resistance (TPR) with exercise was found (p less than 0.01). Pulmonary vascular resistance (PVR) remained unchanged in both subgroups. It is suggested that the value of PVR for subgroup 2 is artificially low because an important variable, namely pulmonary artery wedge pressure, is influenced by alveolar pressure in patients with an uneven distribution of perfusion and ventilation at pulmonary venous pressures lower than alveolar pressure. The steeper slope of the pressure-flow relationship in these patients is probably due to an increased vascular tone caused by chronic hypoxia at rest and further fall of PaO2 and rise of arterial CO2 partial pressure in response to exercise.     

Blood pressure and heart rate variability response to noninvasive ventilation in patients with exacerbations of chronic obstructive pulmonary disease

Sympathetic activation and parasympathetic withdrawal are commonly observed during acute exacerbations of chronic obstructive pulmonary disease (COPD). We have demonstrated previously that noninvasive positive-pressure ventilation (NPPV) improves parasympathetic neural control of heart rate in patients with obstructive sleep apnea. We hypothesized that NPPV may exert such beneficial effects in COPD as well. Therefore, we assessed the acute effects of NPPV on systemic blood pressure and indexes of heart rate variability (HRV) in 23 patients with acute exacerbations of COPD. The measurements of HRV in the frequency domain were computed by an autoregressive spectral technique. The use of NPPV resulted in significant increases of oxygen saturation (from 89.2+/-1.0 to 92.4+/-0.9 %, p<0.001) in association with reductions in systolic and diastolic blood pressures and heart rate (from 147+/-3 to 138+/-3 mm Hg, from 86+/-2 to 81+/-2 mm Hg, from 85+/-3 to 75+/-2 bpm, p<0.001 for all variables), and increases in ln-transformed high frequency band of HRV (from 6.4+/-0.5 to 7.4+/-0.6 ms(2)/Hz, p<0.01). Reductions in heart rate and increases in ln-transformed HF band persisted after NPPV withdrawal. In conclusion, these findings suggest that NPPV may cause improvements in the neural control of heart rate in patients with acute exacerbations of COPD.     

Association of mast cells with lung function in chronic obstructive pulmonary disease

Background

Surfactant protein D (SP-D), an innate immune molecule, plays an important protective role during airway inflammation. Deficiency of this molecule induces emphysematous changes in murine lungs, but its significance in human COPD remains unclear.

Methods

We collected bronchoalveolar lavage fluid from 20 subjects with varying degrees of COPD (8 former smokers and 12 current smokers) and 15 asymptomatic healthy control subjects (5 never smokers, 3 remote former smokers, and 7 current smokers). All subjects underwent a complete medical history and pulmonary function testing. SP-D was measured by Enzyme-Linked ImmunoSorbent Assay. Statistical analysis was performed using nonparametric methods and multivariable linear regression for control of confounding. The effect of corticosteroid treatment on SP-D synthesis was studied in vitro using an established model of isolated type II alveolar epithelial cell culture.

Results

Among former smokers, those with COPD had significantly lower SP-D levels than healthy subjects (median 502 and 1067 ng/mL, respectively, p = 0.01). In a multivariable linear regression model controlling for age, sex, race, and pack-years of tobacco, COPD was independently associated with lower SP-D levels (model coefficient -539, p = 0.04) and inhaled corticosteroid use was independently associated with higher SP-D levels (398, p = 0.046). To support the hypothesis that corticosteroids increase SP-D production we used type II alveolar epithelial cells isolated from adult rat lungs. These cells responded to dexamethasone treatment by a significant increase of SP-D mRNA (p = 0.041) and protein (p = 0.037) production after 4 days of culture.

Conclusion

Among former smokers, COPD is associated with lower levels of SP-D and inhaled corticosteroid use is associated with higher levels of SP-D in the lung. Dexamethasone induced SP-D mRNA and protein expression in isolated epithelial cells in vitro. Given the importance of this molecule as a modulator of innate immunity and inflammation in the lung, low levels may play a role in the pathogenesis and/or progression of COPD. Further, we speculate that inhaled steroids may induce SP-D expression and that this mechanism may contribute to their beneficial effects in COPD. Larger, prospective studies are warranted to further elucidate the role of surfactant protein D in modulating pulmonary inflammation and COPD pathogenesis.     

Vibration response imaging: a novel noninvasive tool for evaluating the initial therapeutic effect of noninvasive positive pressure ventilation in patients with acute exacerbation of chronic obstructive pulmonary disease

Background

The popular methods for evaluating the initial therapeutic effect (ITE) of noninvasive positive pressure ventilation (NPPV) can only roughly reflect the therapeutic outcome of a patient’s ventilation because they are subjective, invasive and time-delayed. In contrast, vibration response imaging (VRI) can monitor the function of a patient’s ventilation over the NPPV therapy in a non-invasive manner. This study aimed to investigate the value of VRI in evaluating the ITE of NPPV for patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD).

Methods

Thirty-six AECOPD patients received VRI at three time points: before NPPV treatment (T1), at 15 min of NPPV treatment (T2), and at 15 min after the end of NPPV treatment (T4). Blood gas analysis was also performed at T1 and at 2 hours of NPPV treatment (T3). Thirty-nine healthy volunteers also received VRI at T1 and T2. VRI examination at the time point T2 in either the patients or volunteers did not require any interruption of the on-going NPPV. The clinical indices at each time point were compared between the two groups. Moreover, correlations between the PaCO₂ changes (T3 vs T1) and abnormal VRI scores (AVRIS) changes (T2 vs T1) were analyzed.

Results

No significant AVRIS differences were found between T1 and T2 in the healthy controls (8.51 ± 3.36 vs. 8.53 ± 3.57, P > 0.05). The AVRIS, dynamic score, MEF score and EVP score showed a significant decrease in AECOPD patients at T2 compared with T1 (P < 0.05), but a significant increase at T4 compared with T2 (P < 0.05). We also found a positive correlation (R² = 0.6399) between the PaCO₂ changes (T3 vs T1) and AVRIS changes (T2 vs T1).

Conclusions

VRI is a promising noninvasive tool for evaluating the initial therapeutic effects of NPPV in AECOPD patients and predicting the success of NPPV in the early stage.     

血浆N端脑钠肽前体与COPD合并慢性肺源性心脏病患者肺动脉压的相关性分析

目的探讨血浆N端脑钠肽前体与COPD合并慢性肺源性心脏病患者肺动脉压的相关性。方法将我院收治的94例COPD稳定期患者,根据心脏彩超检查明确合并慢性肺心病患者分为观察组46例,单纯COPD患者分为对照组48例,采用化学发光法测定两组患者血浆NT-proBNP水平,心脏彩超检查两组患者右心室前壁厚度、右心室舒张末期内径、左室射血分数、主肺动脉宽度、肺动脉压,并进行比较。结果与对照组比较,观察组血浆NT-proBNP水平明显升高(P0.05),右心室前壁厚度、右心室舒张末期内径、主肺动脉宽度、肺动脉压明显升高(P0.05)。血浆NT-proBNP水平与肺动脉压成明显正相关(r=-0.284,P0.01)。结论 COPD合并慢性肺心病患者血浆NT-proBNP水平升高,有助于评估肺动脉高压的严重程度。     

Frequency dependence of pulmonary compliance and resistance in patients with obstructive lung disease

The frequency dependence of pulmonary compliance and resistance was investigated in 27 patients with obstructive lung disease. Compliance and resistance were determined either by the conventional zero crossing (Cdyn) and isovolume (RL) technique or by a modified Fourier analysis following a smoothing procedure (auto- and cross-correlation function) yielding an effective compliance and resistance, CL and RL. The latter technique was used to calculate CL and RL from the fundamental and third and fourth harmonics present in the flow and transpulmonary pressure signals. Three breathing frequencies were investigated: 0.5, 1, and 2 Hz. Both Cdyn and CL, calculated from the fundamental component, decreased progressively with frequency. However, Cdyn showed less frequency dependence than CL. CL calculated from the harmonics was significantly smaller than CL from the fundamental at the same breathing frequency. RL, as well as RL calculated from the fundamental, tended to increase with frequency. A decline of resistance with frequency became apparent, however, when RL from the fundamental was compared with RL obtained from the corresponding higher order harmonics. These results suggest that the frequency dependence of resistance can be masked by the usual procedure of breathing at several frequencies. Instead the measurements should be performed at a single frequency, for instance spontaneous breathing, by computing resistance from the higher order harmonics present in the breathing signals.     

慢性阻塞性肺疾病患者继发肺部真菌感染的临床分析

目的探讨慢性阻塞性肺疾病(COPD)患者继发肺部真菌感染的临床特点。方法回顾性分析2008年1月到2010年12月安徽医科大学第一附属医院收治的COPD继发肺部真菌感染患者病例,并对其耐药情况进行比较。结果本组199例COPD患者检出白色念珠菌137例(68.84%),光滑念珠菌32例(16.08%),热带念珠菌17例(8.54%),克柔念珠菌9例(4.52%),毛霉菌3例(1.51%),清酒假丝酵母菌1例(0.50%);白色念珠菌检出率有下降趋势,热带念珠菌有上升趋势;196例真菌对伏立康唑、氟康唑、两性霉素B、伊曲康唑、氟胞嘧啶的耐药率分别为3.6%、5.1%、1.0%、8.7%和0;2008年至2010年白色念珠菌和光滑念珠菌耐药率变化差异无统计学意义。结论 COPD患者继发肺部真菌感染病原菌仍以白色念珠菌为主,其次为光滑念珠菌和热带念珠菌;白色念珠菌和光滑念珠菌耐药率无明显改变。     

DNAH5 is associated with total lung capacity in chronic obstructive pulmonary disease

Background

Chronic obstructive pulmonary disease (COPD) is characterized by expiratory flow limitation, causing air trapping and lung hyperinflation. Hyperinflation leads to reduced exercise tolerance and poor quality of life in COPD patients. Total lung capacity (TLC) is an indicator of hyperinflation particularly in subjects with moderate-to-severe airflow obstruction. The aim of our study was to identify genetic variants associated with TLC in COPD.

Methods

We performed genome-wide association studies (GWASs) in white subjects from three cohorts: the COPDGene Study; the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE); and GenKOLS (Bergen, Norway). All subjects were current or ex-smokers with at least moderate airflow obstruction, defined by a ratio of forced expiratory volume in 1 second to forced vital capacity (FEV₁/FVC) <0.7 and FEV₁ < 80% predicted on post-bronchodilator spirometry. TLC was calculated by using volumetric computed tomography scans at full inspiration (TLC_CT). Genotyping in each cohort was completed, with statistical imputation of additional markers. To find genetic variants associated with TLC_CT, linear regression models were used, with adjustment for age, sex, pack-years of smoking, height, and principal components for genetic ancestry. Results were summarized using fixed-effect meta-analysis.

Results

Analysis of a total of 4,543 COPD subjects identified one genome-wide significant locus on chromosome 5p15.2 (rs114929486, β = 0.42L, P = 4.66 × 10⁻⁸).

Conclusions

In COPD, TLC_CT was associated with a SNP in dynein, axonemal, heavy chain 5 (DNAH5), a gene in which genetic variants can cause primary ciliary dyskinesia. DNAH5 could have an effect on hyperinflation in COPD.

Electronic supplementary material

The online version of this article (doi:10.1186/s12931-014-0097-y) contains supplementary material, which is available to authorized users.     

MAPK signaling in the quadriceps of patients with chronic obstructive pulmonary disease

Muscle atrophy in chronic obstructive pulmonary disease (COPD) is associated with reduced exercise tolerance, muscle strength, and survival. The molecular mechanisms leading to muscle atrophy in COPD remain elusive. The mitogen-activated protein kinases (MAPKs) such as p38 MAPK and ERK 1/2 can increase levels of MAFbx/Atrogin and MuRF1, which are specifically involved in muscle protein degradation and atrophy. Our aim was to investigate the level of activation of p38 MAPK, ERK 1/2, and JNK in the quadriceps of patients with COPD. A biopsy of the quadriceps was obtained in 18 patients with COPD as well as in 9 healthy controls. We evaluated the phosphorylated as well as total protein levels of p38 MAPK, ERK 1/2, and JNK as well as MAFbx/Atrogin and MuRF1 in these muscle samples. The corresponding mRNA expression was also assessed by RT-PCR. Ratios of phosphorylated to total level of p38 MAPK (P = 0.02) and ERK 1/2 (P = 0.01) were significantly elevated in patients with COPD compared with controls. Moreover, protein levels of MAFbx/Atrogin showed a tendency to be greater in patients with COPD (P = 0.08). mRNA expression of p38 MAPK (P = 0.03), ERK 1/2 (P = 0.02), and MAFbx/Atrogin (P = 0.04) were significantly elevated in patients with COPD. In addition, phosphorylated-to-total p38 MAPK ratio (Pearson's r = -0.45; P < 0.05) and phosphorylated-to-total ERK 1/2 ratio (Pearson's r = -0.47; P < 0.05) were negatively associated with the mid-thigh muscle cross-sectional area. These data support the hypothesis that the MAPKs might play a role in the development of muscle atrophy in COPD.     

Proteinases in chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is a major health problem worldwide, and we have little specific therapy to offer these patients. One potential strategy to limit loss of lung function in COPD would be to inhibit matrix-degrading proteinases. Several serine proteinases and matrix metalloproteinases are expressed in association with COPD in humans. Application of gene-targeted macrophage elastase and neutrophil elastase to a mouse model of cigarette-smoke-induced emphysema has uncovered roles for these proteinases in airspace enlargement, and has identified many interactions between these proteolytic systems.     

Regenerative defect in vastus lateralis muscle of patients with chronic obstructive pulmonary disease

Background

Impaired skeletal muscle regeneration could contribute to the progression of muscle atrophy in patients with chronic obstructive pulmonary disease (COPD).

Methods

Satellite cells and myogenesis-related proteins were compared between healthy subjects and patients with COPD, with or without muscle atrophy. Satellite cells were isolated and cultured to assess their proliferative and differentiation aptitudes.

Results

Although satellite cell numbers in muscle samples were similar between groups, the proportion of muscle fibers with central nuclei was increased in COPD. In muscle homogenates, increased expression of MyoD and decreased expression of myogenin and MRF4 were observed in COPD. In cultured satellite cells of patients with COPD, increased protein content was observed for Pax7, Myf5 (proliferation phase) and myogenin (differentiation phase) while myosin heavy chain protein content was significantly lower during differentiation.

Conclusion

In COPD, the number of central nuclei was increased in muscle fibers suggesting a greater number of attempts to regenerate muscle tissue than in healthy subjects. Myogenesis signaling was also altered in muscle homogenates in patients with COPD and there was a profound reduction in the differentiation potential in this population as indicated by a reduced ability to incorporate myosin heavy chain into newly formed myotubes. Collectively, these results indicate that skeletal muscle regenerative capacity termination is impaired in COPD and could contribute to the progression of muscle atrophy progression in this population.     

Cellular and cytokine immunoregulation in patients with chronic obstructive pulmonary disease and bronchial asthma

BACKGROUND: Different forms of chronic airway inflammation may involve diverse pathogenic elements. In general, deficient defence response is a feature of chronic obstructive pulmonary disease (COPD), whereas distorted immunoregulatory mechanisms lead to development of asthmatic symptoms. In addition to diverse effector mechanisms, the cellular and humoral elements participating in the development of immune response may appear to be different in COPD and bronchial asthma (BA) patients. AIMS: To evaluate the immunoregulatory properties of T cells and monocytes in cultures of peripheral blood mononuclear cells (PBMC) and to determine the chosen cytokine profiles in COPD and BA patients. METHODS: The microcultures of PBMC from COPD and BA patients were assessed for the T-cell response to mitogens, saturation of interleukin (IL)-2 receptors, T-cell suppressive activity and monokine influence on lymphocyte proliferation. Concomitantly, the cytokine (IL-1beta, interleukin-1 receptor antagonist, tumour necrosis factor-alpha, IL-4, IL-6, IL-8) concentrations were determined in the serum, the broncho-alveolar lavage fluid and in the culture supernatants. RESULTS: The T-lymphocyte reactions (response to phytohaemagglutinin, IL-2 receptor saturation, suppressive activity) were lower in BA patients than in COPD patients. Reversely, the immunogenic activity of monocytes (IL-1beta versus IL-1ra production) was higher in BA patients than in COPD patients. The highest values of cytokine concentrations were found in the culture supernatants. The concentrations of tumour necrosis factor-alpha, IL-4, IL-6 and IL-8 were significantly higher and the concentration of IL-1ra was lower in BA patients than in COPD patients. CONCLUSION: The assessments of cellular immunoregulatory properties and cytokine profiles in the cultures of blood mononuclear cells may prove helpful for diagnostic and therapeutic discrimination between BA and COPD patients.     

Two-year home-based nocturnal noninvasive ventilation added to rehabilitation in chronic obstructive pulmonary disease patients: A randomized controlled trial

Background

The use of noninvasive intermittent positive pressure ventilation (NIPPV) in chronic obstructive pulmonary disease (COPD) patients with chronic hypercapnic respiratory failure remains controversial as long-term data are almost lacking.The aim was to compare the outcome of 2-year home-based nocturnal NIPPV in addition to rehabilitation (NIPPV + PR) with rehabilitation alone (PR) in COPD patients with chronic hypercapnic respiratory failure.

Methods

Sixty-six patients could be analyzed for the two-year home-based follow-up period. Differences in change between the NIPPV + PR and PR group were assessed by a linear mixed effects model with a random effect on the intercept, and adjustment for baseline values. The primary outcome was health-related quality of life (HRQoL); secondary outcomes were mood state, dyspnea, gas exchange, functional status, pulmonary function, and exacerbation frequency.

Results

Although the addition of NIPPV did not significantly improve the Chronic Respiratory Questionnaire compared to rehabilitation alone (mean difference in change between groups -1.3 points (95% CI: -9.7 to 7.4)), the addition of NIPPV did improve HRQoL assessed with the Maugeri Respiratory Failure questionnaire (-13.4% (-22.7 to -4.2; p = 0.005)), mood state (Hospital Anxiety and Depression scale -4.0 points (-7.8 to 0.0; p = 0.05)), dyspnea (Medical Research Council -0.4 points (-0.8 to -0.0; p = 0.05)), daytime arterial blood gases (PaCO₂ -0.4 kPa (-0.8 to -0.2; p = 0.01); PaO₂ 0.8 kPa (0.0 to 1.5; p = 0.03)), 6-minute walking distance (77.3 m (46.4 to 108.0; p < 0.001)), Groningen Activity and Restriction scale (-3.8 points (-7.4 to -0.4; p = 0.03)), and forced expiratory volume in 1 second (115 ml (19 to 211; p = 0.019)). Exacerbation frequency was not changed.

Conclusions

The addition of NIPPV to pulmonary rehabilitation for 2 years in severe COPD patients with chronic hypercapnic respiratory failure improves HRQoL, mood, dyspnea, gas exchange, exercise tolerance and lung function decline. The benefits increase further with time.

Trial registration

ClinicalTrials.Gov (ID NCT00135538).     

Eotaxin in serum of patients with asthma or chronic obstructive pulmonary disease: relationship with eosinophil cationic protein and lung function

This study was undertaken to investigate the correlation between the serum ECP and the serum eotaxin level, and disease activity as evaluated with pulmonary function in patients with asthma or chronic obstructive pulmonary disease (COPD). 20 patients with stable asthma and 15 patients with COPD, and 15 subjects of the control group took part in this study. The analysis of ECP was performed according to the manufacturer's directions (Pharmacia Diagnostics AB, Uppsala, Sweden). The ELISA test was used to measure eotaxin levels in sserum (kits from R&D, USA). The levels of ECP were 16.9+/-6.3 microg/L in patients with asthma, 15.1+/-9.3 microg/L in patients with COPD and 11.8+/-6.2 microg/L in the control group (P<0.05). There was no significant difference in the asthma ECP level compared with the ECP level in COPD. There was a significant difference between the ECP plasma level in asthma compared with the ECP plasma level in the control group (p<0.05). The levels of eotaxin were 175.8+/-49.3 pg/mL in the control group. There was a correlation of ECP and the eotaxin level in asthma patients (r=+0.5, p<0.05). The percentage fall in FEV1 correlated with eotaxin level in asthma (r=-0.3, p<0.05) and with the eotaxin level in COPD (r=-0.5, p<0.05). Serum outcomes of eotaxin and ECP levels appear to be a useful indicator of atopic asthma, and might provide complementary data disease monitoring. Therefore, further investigations are required to clarify whether serum eotaxin measurements have a role in the clinical evaluation in COPD.     

Power spectral density of breathing pattern in patients with chronic obstructive lung disease

Newsom Davis and Stagg studying the interrelationship of the volume and time components of individual breaths in healthy resting man described a significant correlation between mean tidal volume (VT) and inspiratory time (TI) r = 0.704. The correlation between mean TI and expiratory time (TE) was lower, r = 0.381. Evaluation of these relationships and of the power spectral density of the breathing pattern was the aim of the present study. For breath by breath analysis we calculated power spectral density and cross correlations of VT, TI and TE. We found a significant correlation between VT and TI in 9 patients with global respiratory insufficiency (RI) (mean r = 0.52) and 7 patients with partial RI (mean r = 0.56). The correlation between TI, TE was lower, in 9 patients with global RI (mean r = 0.21) and 7 patients with partial RI (mean r = 0.35). The results of both groups did not differ from healthy subjects in power spectral density of the breathing pattern and in correlations of VT and TI as well as TI and TE.     

Criteria of fitness for anaesthesia in patients with chronic obstructive lung disease.

Twelve patients with severe chronic obstructive lung disease undergoing 15 operations were assessed with preoperative lung function tests and blood gas estimations. Their operative and postoperative course was followed. There were no deaths or serious complications. Patients fell into three groups: those with low respiratory capacity but normal blood gases, who required no special respiratory treatment apart from physiotherapy and antibiotics; those with hypoxaemia but normal arterial carbon dioxide pressure, who needed more prolonged oxygen treatment after operation; and those with hypoxaemia and hypercapnia, who needed postoperative ventilatory support. While forced expiratory volume in one second (FEV) is a good screening test in preoperative assessment it should be supplemented by arterial blood gas estimations in patients with an FEV of less than 1 litre.