Efficacy evaluation of Qingyan formulation in a smoking environment and screening of anti-inflammatory compounds.

Qingyan formulation (QF) is a common preparation that is often used to control inflammation in the haze environment. However, the efficacy and effective constituents of QF are still uncertain and difficult to identify. This paper aims to evaluate the efficacy by simulating a haze environment and determine its anti-inflammatory compounds by UPLC/Q-TOF-MS/MS combing with bioactivity screening. The therapeutic effect of QF in the simulated haze environment was confirmed from the aspects of lung histomorphology and inflammatory factor expression levels. QF showed strong anti-inflammatory activity with the minimum effective concentration reaching 1.5 g/kg. Potential anti-inflammatory components were screened by the NF-κB activity assay system and simultaneously identified based on mass spectral data. Then, the potential active compounds were verified by molecular biological methods, the minimum effective concentration can reach 0.1 mg/L. Six structural types of NF-κB inhibitors (phenolic acid, scopolamine, hydroxycinnamic acid, flavonoid, dihydroflavone and steroid) were identified. Further cytokine assays confirmed their potential anti-inflammatory effects of NF-κB inhibitors. This strategy clearly demonstrates that QF has a significant therapeutic effect on respiratory diseases caused by haze, so it is necessary to promote its commercialization and wider application.

The effects of nodakenin on airway inflammation, hyper-responsiveness and remodeling in a murine model of allergic asthma.

CONTEXT: Nodakenin is a major coumarin glucoside in the root of Peucedanum decursivum Maxim, a commonly used traditional Chinese medicine for the treatment of asthma and chronic bronchitis for thousands of years. OBJECTIVE: In this work, the anti-asthma potential of nodakenin was studied by investigation of its effect to suppress airway inflammation, hyper-responsiveness and remodeling in a murine model of chronic asthma. MATERIALS AND METHODS: BALB/c mice sensitized to ovalbumin (OVA) were challenged with aerosolized OVA for 8 weeks, orally administered with nodakenin at doses of 5, 10 and 20 mg/kg before each OVA challenge. RESULTS: Compared with the model group, nodakenin treatment markedly inhibited airway inflammation, hyper-responsiveness and remodeling, showing improvement in subepithelial fibrosis, smooth muscle hypertrophy, and goblet cell hyperplasia, and decreased levels of interleukin (IL)-4, IL-5, IL-13 and matrix metalloproteinase-2/-9 in bronchoalveolar lavage fluid, and the level of OVA-specific IgE in serum. In addition, the NF-κB DNA-binding activity in lung tissues was also reduced by nodakenin treatment. CONCLUSIONS: These data indicated that nodakenin might mitigate the development of chronic experimental allergic asthma.

Positioning of the Bronchitis Severity Score (BSS) for standardised use in clinical studies.

OBJECTIVE: Diagnosis and assessment of response to treatment in acute bronchitis depends on clinical findings. We evaluated published data on the Bronchitis Severity Score (BSS) used to diagnose acute bronchitis and to evaluate the impact of treatment in clinical studies. METHODS: We conducted a literature search using PubMed (search terms: acute bronchitis, treatment, score, and BSS; publication date April 2012 or earlier) and asked the manufacturer for relevant publications. Articles were reviewed and relevant studies were classified according to author, study design, measurements made and duration of study, study drug(s), outcome, and statistical significance. RESULTS: The medication most frequently evaluated by the BSS is a herbal drug preparation from the roots of Pelargonium sidoides (EPs 7630). The BSS consistently demonstrated statistically significant differences between active treatments and placebo as well as between different doses of active treatment. The proportion of responders was considerably higher in the EPs 7630 group than in the placebo group. Because of the subjective components of the BSS, inter-individual differences in results may exist. However, the BSS outcome was supported by the results of secondary outcome measures, such as the Integrated Medicine Patient Satisfaction Scale (IMPSS), documenting that patients were more often 'satisfied' or 'very satisfied' with EPs 7630 than placebo. CONCLUSIONS: We recommend further use of the BSS as a reliable and convenient clinical trial tool for selecting and evaluating patients in studies of acute bronchitis. Improvement in the BSS correlates with outcomes reported by these patients.

[Effect of earthworm decoction on airway inflammation of bronchial asthma in guinea pigs].

OBJECTIVE: To investigate the effect of Earthworm decoction on the airway inflammation of experimental bronchial asthma in guinea pigs and inquire into the mechanism in the decoction. METHOD: Forty-eight guinea pigs were randomly divided into six groups: the control group, the model group, the dexamethasone group, the Xiaoqinglong decoction group, the earthworm decoction large dosage group and the Earthworm decoction low dosage group, 8 guinea pigs in each group. Except the control group, the other groups were sensitized with ovalbumin (OVA) by a combination of intraperitional injection and repeated intranasal challenges to establish the guinea pigs asthma model. However, in the control group, normal saline was used. The morphological changes of bronchial tube, the lung tectology and the inflammation germ cell quantity of eosinophils (Eos), lymphocytes (Ly), neutrophils (Neu) and total blood cells in the blood and bronchoalveolar lavaga fluid (BALF) were examinated in each group respectively. RESULT: The levels of Eos, Ly, Neu and total cell quantity in the blood and BALF after the earthworm decoction treatment in the large dosage group were significantly lower than those in the model group (P <0.01), and in the low dosage group were lower too (P <0.05). The Earthworm decoction large dosage could obviously improve the bronchial tube epidermis damage, the mucous membrane gland proliferation and hydrops, asthma pathology change and basilar membrane accumulation. Eos apoptosis was obsered in the bronchoalveolar, blood and BALF. The Earthworm decoction small dosage had a similar effect but slightly to the large dosage. CONCLUSION: The Earthworm decoction can lighten the airway inflammation in asthmatic guinea pigs, its mechanism is related with the inhibition of Eos infiltration, acceleration of Eos apoptosis and improvement of the bronchial tube and the lung tectology changes. The effect of the decoction is dose-dependent.

Pelargonium sidoides preparation (EPs 7630) in the treatment of acute bronchitis in adults and children.

Acute bronchitis, although mostly caused by viral infections, is commonly treated with antibiotics. As antibiotics should only be prescribed upon strict indication, treatment options like a liquid herbal drug preparation from the roots of Pelargonium sidoides (EPs 7630) gain more and more interest. To evaluate the efficacy and safety of treatment with EPs 7630 in patients with acute bronchitis, a multi-centre, prospective, open observational study was conducted in 440 study sites located in Germany. A total of 2099 patients aged 0-93 years with productive cough for less than six days without indication for treatment with antibiotics were given EPs 7630-solution in an age-dependent dosage for 14 days. The primary outcome criterion was the mean change of the Bronchitis Severity Score (BSS: cough, sputum, rales/rhonchi, chest pain at cough, dyspnoea) from baseline to patient's individual last observation. During treatment, the mean BSS of all patients decreased from 7.1+/-2.9 points at baseline to 1.0+/-1.9 points at patients' individual last visit. Subgroup analysis for children showed a decrease of mean BSS from 6.3+/-2.8 points to 0.9+/-1.8 points and analysis of children younger than three years showed a decrease of mean BSS from 5.2+/-2.5 points to 1.2+/-2.1 points. Adverse events occurred in 26/2099 (1.2%) patients. Serious adverse events were not reported. In conclusion, EPs 7630 is an effective and well tolerated treatment of acute bronchitis in adults, children and infants outside the strict indication for antibiotic treatment.

Treatment effect and safety of EPs 7630-solution in acute bronchitis in childhood: report of a multicentre observational study.

An open post-marketing surveillance study was conducted to examine the treatment effect and safety of EPs 7630-solution in the treatment of acute bronchitis in children. This study included a total of 742 children (aged between 0 and 12 years) with acute bronchitis (83.4%) or acute exacerbations of chronic bronchitis (14.3%), who were treated with different doses of the herbal drug for up to 14 days. Five bronchitis specific symptoms (BSS) were summed up to give an overall measure of disease severity. Non-specific disease symptoms (loss of appetite, diarrhoea, headache, vomiting, and fever) were also recorded, together with adverse events and overall ratings of efficacy and tolerability. The overall BSS score decreased during treatment from 6.0+/-3.0 points at baseline to 2.7+/-2.5 points after 7 days and to 1.4+/-2.1 points after 14 days. Remission or improvement in at least 80% of patients was recorded for all the individual component symptoms. The proportion of patients suffering from non-specific symptoms also substantially improved during treatment. For example, loss of appetite was present in 65.8% of patients at study begin, but only in 27.6% at the time point of last observation visit. In 88.3% of cases, the responsible physician rated the treatment as successful. Adverse events were minor and transitory. In conclusion, EPs 7630-solution was shown to be a safe and an effective treatment option for acute bronchitis or acute exacerbations of chronic bronchitis in children.

EPs 7630-solution--an effective therapeutic option in acute and exacerbating bronchitis.

Acute bronchitis is one of the most common diagnoses in ambulatory care medicine. Although the benefit of antibiotics for acute bronchitis, which is mostly virally induced, is disputed, they are often prescribed. A therapeutic option for respiratory tract infections that do not fall within the strict indication range for antibiotic administration is the liquid herbal drug preparation from the roots of Pelargonium sidoides, EPs 7630 (Umckaloabo), which has been tested against placebo in double-blind clinical trials. EPs 7630 has both antibacterial and immuno-modulating properties. The efficacy and tolerability of EPs 7630 was investigated in a prospective, open, multicentric outcomes study with 205 patients suffering from acute bronchitis or acute exacerbation of chronic bronchitis. The main outcome measure was the change in the total score of five symptoms typical for bronchitis (cough, expectoration, wheezing/whistling on expiration, chest pain during coughing, and dyspnoea), which were each rated using a 5-point scale (from 0=not present to 4=extremely pronounced). Further symptoms (hoarseness, headache, aching limbs and fatigue) were assessed using a four-point scale (from 0=not present to 3=very pronounced). The total score of the typical bronchitis symptoms amounted to 6.1+/-2.8 points on average at the start of treatment and decreased by 3.3+/-3.8 points to 2.8+/-2.6 points by the final examination on day 7. About 60.5% of the patients assessed their health condition at the end of the study as much improved or free from symptoms. The onset of action appeared after two days on average. Adverse events occurred in a total of 16 patients. There were no serious adverse events. Altogether, 78% of the patients were satisfied or very satisfied with the treatment.

Prednisone blunts airway neutrophilic inflammatory response due to ozone exposure in asthmatic subjects.

BACKGROUND: The effect of corticosteroids on the ozone (O3)-induced airway inflammation is still debated. OBJECTIVE: The aim of the study was to confirm the effect of a short-term treatment with oral glucocorticosteroids on O3-induced airway inflammation, detected by induced sputum analysis, and on functional response in glucocorticosteroid-naive subjects. METHODS: A randomized, placebo-controlled study using oral prednisone (25 mg o.d. for 4 days) was carried out. Nine mild persistent asthmatics were exposed for 2 h, on separatedays, to 0.27 ppm O3 and to air in random order, after 4 days of treatment with prednisone (25 mg o.d.) and after 4 days of placebo.Before and after exposure, pulmonary function test was measured; 6 h afterexposure, sputum induction was done. RESULTS: Oral glucorticosteroids did not prevent pulmonary function decrement due to O3. After placebo, the percentage of neutrophils in induced sputum was significantly higher after O3 than after air [52.1 (15.7-77.3) vs. 17.8 (1.7-58.4), p=0.02, O3 vs. air]. This difference was lost after 4 days of treatment with prednisone [35.2% (10-96.2) vs. 30.9% (6.1-75.6), n.s., O3 vs. air]. Neutrophil elastase in sputum supernatant increased after O3 exposure in the sample obtained after placebo, but not after prednisone treatment. CONCLUSIONS: This study confirms that glucocorticosteroids reduce inflammatory airway response, but do not prevent the airway functional impairment after O3 exposure.

Ganoderma tsugae supplementation alleviates bronchoalveolar inflammation in an airway sensitization and challenge mouse model.

Ganoderma tsugae (a Chinese mushroom Songshan lingzhi) cultivated in Taiwan is extensively used in Chinese traditional medicine to treat different diseases. To determine whether G. tsugae has anti-inflammatory effects on bronchoalveolar inflammation in vivo, we investigated the anti-inflammatory effects of G. tsugae products, YK01 and YK07, on bronchoalveolar inflammation using an airway sensitization and challenge mouse model. Female BALB/c mice were weekly sensitized by intraperitoneal injection of ovalbumin (OVA) three times and challenged with aerosolized OVA twice. Differential cell counts of infiltrating leukocytes, inflammatory mediators, cytokines in bronchoalvelor lavage fluid (BALF) of OVA-challenged mice were examined after continuously consuming G. tsugae diets for 5 weeks. We found that supplementation of G. tsugae significantly decreased total infiltrating leukocytes and lymphocyte percentage in BALF in the experimental groups. Supplementation of G. tsugae also significantly reduced inflammatory mediators in BALF including histamine, prostaglandin E2, eotaxin, and protein levels, however the levels of pro-inflammatory cytokines, interleukin (IL)-1beta and IL-6, in BALF did not significantly change. These results suggest that both G. tsugae supplementation diets YK01 and YK07 might alleviate bronchoalveolar inflammation via decreasing the infiltration of inflammatory cells and the secretion of inflammatory mediators into the local tissues of lungs and airways. Further, these results indicate that the relief of bronchoalveolar inflammation in an airway sensitization murine model provides a possible therapeutic application for G. tsugae in allergic asthma.

Efficacy and safety of an extract of Pelargonium sidoides (EPs 7630) in adults with acute bronchitis. A randomised, double-blind, placebo-controlled trial.

BACKGROUND: New evidence-based treatment options are required to avoid antibiotic overuse in acute bronchitis and to replace potentially inefficacious initial antibiotic treatment. OBJECTIVE: To evaluate the efficacy and safety of an extract of Pelargonium sidoides (EPs 7630) compared to placebo in patients with acute bronchitis. DESIGN: Randomized, double-blind, placebo-controlled trial using a multi-stage adaptive design. SETTING: 36 primary care physicians (investigators) at the out-patient care setting. PATIENTS: 468 adults with acute bronchitis present < or = 48 hours, Bronchitis Severity Score (BSS) > or = 5 points, and informed consent. INTERVENTION: EPs 7630 or placebo (30 drops three times daily) for 7 days. MEASUREMENT: The primary outcome criterion was the change of BSS on day 7. RESULTS: The decrease of BSS from baseline to day 7 was 5.9 +/- 2.9 points under EPs 7630 (n = 233), and 3.2 +/- 4.1 points under placebo (n = 235). The 95% CI for the difference of effects between the two treatment groups (EPs 7630 minus placebo) was calculated as [-3.359; -2.060] showing a significant superiority of EPs 7630 compared to placebo on day 7 (p < 0.0001). Working inability decreased to 16% in the EPs 7630 group compared to 43% in the placebo group (p < 0.0001). In addition, the duration of illness was significantly shorter for patients treated with EPs 7630 compared to placebo (p < 0.001). Within the first four days, onset of treatment effect was recognized in 53.6% of patients under EPs 7630 compared to 36.2% of patients under placebo, only (p < 0.0001). Adverse events (AEs) occurred in 36/468 patients (EPs 7630: 20/233 patients, placebo: 16/235 patients). All events were assessed as non-serious. CONCLUSION: EPs 7630 was superior in efficacy compared to placebo in the treatment of adults with acute bronchitis. Treatment with EPs 7630 clearly reduced the severity of symptoms and shortened the duration of working inability for nearly 2 days.

IL-10 reduces Th2 cytokine production and eosinophilia but augments airway reactivity in allergic mice.

We investigated the effects of interleukin (IL)-10 administration on allergen-induced Th2 cytokine production, eosinophilic inflammation, and airway reactivity. Mice were sensitized by intraperitoneal injection of ragweed (RW) adsorbed to Alum and challenged by intratracheal instillation of the allergen. Sensitization and challenge with RW increased concentrations of IL-10 in bronchoalveolar lavage (BAL) fluid from undetectable levels to 60 pg/ml over 72 h. Intratracheal instillation of 25 ng of recombinant murine IL-10 at the time of RW challenge further elevated BAL fluid IL-10 concentration to 440 pg/ml but decreased BAL fluid IL-4, IL-5, and interferon-gamma levels by 40-85% and eosinophil numbers by 70% (P < 0.0001). Unexpectedly, the same IL-10 treatment increased airway reactivity to methacholine in spontaneously breathing mice that had been sensitized and challenged with RW (P < 0.001). IL-10 treatment in naive animals or RW-sensitized mice challenged with PBS failed to increase airway reactivity, demonstrating that IL-10 induces an increase in airway reactivity only when it is administered in conjunction with allergic sensitization and challenge. The results demonstrate that IL-10 reduces Th2 cytokine levels and eosinophilic inflammation but augments airway hyperreactivity. Thus, despite its potent anti-inflammatory activity, IL-10 could contribute to the decline in pulmonary function observed in asthma.

[Effects of nitric oxide on the airway inflammation and lymphocyte proliferation in sensitized rats].

OBJECTIVE: To investigate the relations between intrinsic nitric oxide (NO) and airway inflammation and lymphocyte proliferation in bronchial asthma. METHOD: The rat model of asthmatic airway inflammation was established by first sensitizing and then challenging the animals with ovalbumin. NO synthase (NOS) inhibitor and NO precursor were then applied and their influences on the airway inflammatory cell numbers and on the numbers of mIL-2R positive lymphocytes were observed. RESULT: In vivo experiments showed that normal control rats (n = 6) did not have eosinophils in their submucosal of airways while in the sensitized animals (n = 6) eosinophils [23 +/- 5 (average cell counts per microscopic visual field, the same below) as well as lymphocytes (34 +/- 5) and mIL-2R positive cells (12 +/- 3) were found in significantly increased numbers in the airways. The application of NOS inhibitor significantly reduced eosinophils (13 + 3, P < 0.05) and mIL-2R positive cells (4.3 +/- 1.6, P < 0.05) in the sensitized animals and the number of lymphocytes was also decreased (28 +/- 4) although it did not reach the significant level. At the same time the spleen cell proliferation was inhibited (P < 0.05) and the mIL-2R positive spleen cell numbers were reduced (P < 0.05). On the contrary, the application of NO precursor resulted in the further increase of the numbers of eosinophils, lymphocytes and mIL-2R positive cells although the differences were not statistically significant. In vitro experiments showed that NOS inhibitor inhibited the proliferation of cultured spleen lymphocytes as well as their mIL-2R expression (P < 0.05). NO precursor, when used in low dose, could promote the proliferation and mIL-2R expression of spleen cells (P < 0.05); but high dose of it showed inhibiting effect on the spleen cells (P < 0.05). CONCLUSION: Intrinsic NO at a suitable level is important in the regulation of the proliferation and activation of lymphocytes in the airways with allergic inflammation in the sensitized rats. This research is conducive to the understanding of the pathogenesis of the asthmatic airway inflammation and to investigating of new therapeutic approaches.

Intraluminal inflammation in the airways of patients with chronic bronchitis after treatment with Ambroxol.

Ambroxol is a mucus-modifying drug with a known ability to stimulate surfactant secretion and inhibit, in vitro, the production of proinflammatory cytokines, neutrophil chemotaxis, and Na+ absorption by the airway epithelium. In dogs inhaling ozone, bronchial hyperreactivity can be inhibited by aerosolized Ambroxol. To verify the possibility of producing anti-inflammatory effects in a clinically relevant condition, 20 patients with chronic bronchitis, randomly divided into two balanced matched groups, were submitted to a 14 day trial with Ambroxol, 150 mg.day-1, or placebo, according to a double-blind design. A bronchoalveolar lavage (BAL) was performed the day before starting treatment (T0) and at the 14th day (T14). The analysis of the cellular and soluble (total proteins, albumin, immunoglobulin G and A (IgG and IgA)) BAL components demonstrated no clear modifications. In particular, neutrophil values from the bronchial aliquot showed a large dispersion, with no significant differences (Ambroxol: T0 = 13.7 +/- 5.2%, T14 = 14.0 +/- 6.8%; placebo: T0 = 3.6 +/- 1.1%, T14 = 5.5 +/- 2.2%). We found a nonsignificant increase of phospholipids in BAL supernatants from Ambroxol-treated patients (2.5 +/- 1.9 vs 3.0 +/- 1.9 micrograms.mg-1 of protein); whilst in the placebo group data before and after treatment were superimposable (2.2 +/- 1.5 vs 2.3 +/- 1.9 micrograms.mg-1 of protein). In conclusion, we have failed to demonstrate that conventional treatment with oral Ambroxol can modify surfactant and BAL cell populations in the airways of patients with chronic bronchitis.

[Treatment of patients with chronic obstructive bronchitis]. / Sposob lecheniia bolnykh khronicheskim obstruktivnym bronkhitom.

As shown in a trial in 172 patients with chronic obstructive bronchitis suffering from respiratory trouble, chronic cor pulmonale, circulatory insufficiency, combined application of electrical stimulation of the diaphragm with ultrasonic inhalations is much more effective than separate use of these two modalities which, when used together, potentiate positive and abate side effects of each other. The method is simple in application, reduces the duration of the hospital stay, prevents incapacitation.

[Experimental study of modified yu ping feng powder on antibacterial adhesion of tracheal mucosa in mice model of chronic bronchitis].

In order to observe the influence of modified Yu Ping Feng San (MYPFS) on bacterial adhesion of tracheal mucosa, four experiments of bacterial adhesion in pneumatic tract were conducted, in which mice of chronic bronchitis model (CBM) induced by SO2 stimulation and another health control group breathed in aerosol contained Pseudomonas aeruginosa under the same condition were observed. The results showed that, with scanning electron microscopy, ultrastructural lesions on tracheal mucosa surface and adhesive bacterial number in CBM administrated MYPFS were far less than that in CBM without MYPFS (P < 0.001), and quantitative culture of Pseudomonas aeruginosa with tracheal tissue homogenate was also markedly reduced. However, the tracheal mucosa of healthy control animals were intact, the adhesive bacteria were not found. It is suggested that bacterial adhesion was closely related to the injury of tracheal-mucosa, and MYPFS could play a role of anti-bacterial adhesion through the protection of tracheal mucosa epithelium or reduction of pneumatic tract injury. These were quite in accordance with the theories of traditional Chinese medicine in "strengthening body resistance to eliminate the pathogenic factor", so that they provided experimental evidence for TCM tonics to prevent and treat infection of respiratory tract.

Bronquitis cronica: clinica y orientaciones sobre su tratamiento homeopatico / Chronic bronquitis: clinic and orientations about its homeopathic treatment

Proceso caracterizado por la presencia de tos productiva tres meses consecutivos de cada ano; el sexo masculino se afecta mas que el femenino siendo el factor predisponente mas importante el tabaquismo. Se presentan estertores roncantes gruesos y sibilancias que cambian de intensidad y localizacion, y signos de Cor pulmonale cronico. La fisiopatologia indica aumento en la resistencia de las vias aereas y disminucion de los indices maximos de flujo respiratorio. Como parte importante del tratamiento se indica dejar el tabaco. El tratamiento racional complementa las medidas generales con la terapeutica homeopatica en cada una de las fases de este padecimiento

Bronquitis cronica: clinica y orientaciones sobre su tratamiento homeopatico / Chronic bronquitis: clinic and orientations about its homeopathic treatment

Proceso caracterizado por la presencia de tos productiva tres meses consecutivos de cada ano; el sexo masculino se afecta mas que el femenino siendo el factor predisponente mas importante el tabaquismo. Se presentan estertores roncantes gruesos y sibilancias que cambian de intensidad y localizacion, y signos de Cor pulmonale cronico. La fisiopatologia indica aumento en la resistencia de las vias aereas y disminucion de los indices maximos de flujo respiratorio. Como parte importante del tratamiento se indica dejar el tabaco. El tratamiento racional complementa las medidas generales con la terapeutica homeopatica en cada una de las fases de este padecimiento

[Changes in the bronchial tree under the influence of pelotherapy in patients with pulmonary tuberculosis]. / Izmeneniia bronkhial'nogo dereva pod vliianiem peloidoterapii u bol'nykh tuberkulezom legkikh.

It was shown with using the clinical materials relating to 400 patients with pulmonary tuberculosis that peloids such as humisole, torfot and peloidin used in combination with antituberculous drugs had a favourable effect on involution of specific and nonspecific processes in the bronchi and restoration of bronchial patency. This also permitted a decrease in the terms for elimination of inflammatory lesions in the tracheobronchial tree. Phonophoresis with peloidin proved to be the most efficient procedure of pelotherapy since its use provided summation of the therapeutic effects of the mud preparation and ultrasound vibrations as well as local action on the affected organ.

Athletic training in chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a common and very debilitating disease in the United States. COPD is characterized by plugging of airways with secretions, impaired airway integrity with airway collapse with effort, bronchospasm, frequent infections, destruction of alveolar tissue, and ventilation-to-perfusion inequality. This results in abnormalities in pulmonary mechanics and respiratory gas exchange, all of which make hyperventilation much less effective. However, research has shown that the pulmonary patient can improve work capacity in an exercise training program. Training also alleviates the severe emotional problems of anxiety, depression, and social isolation frequently present in COPD sufferers. Even the lowest level patient can frequently improve in a training program, and guidelines for the implementation of such a therapeutic regimen are provided.