Impact of airflow limitation in chronic heart failure

Background

Comorbidities are common in chronic heart failure (HF) patients, but diagnoses are often not based on objective testing. Chronic obstructive pulmonary disease (COPD) is an important comorbidity and often neglected because of shared symptoms and risk factors. Precise prevalence and consequences are not well known. Therefore, we investigated prevalence, pulmonary treatment, symptoms and quality of life (QOL) of COPD in patients with chronic HF.

Methods

205 patients with stable HF for at least 1 month, aged above 50 years, were included from our outpatient cardiology clinic, irrespective of left ventricular ejection fraction. Patients performed post-bronchodilator spirometry, a six-minute walk test (6-MWT) and completed the Kansas City Cardiomyopathy Questionnaire (KCCQ). COPD was diagnosed according to GOLD criteria. Restrictive lung function was defined as FEV₁/FVC ≥0.70 and FVC <80% of predicted value. The BODE and ADO index, risk scores in COPD patients, were calculated.

Results

Almost 40% fulfilled the criteria of COPD and 7% had restrictive lung disease, the latter being excluded from further analysis. Noteworthy, 63% of the COPD patients were undiagnosed and 8% of those without COPD used inhalation therapy. Patients with COPD had more shortness of breath despite little difference in HF severity and similar other comorbidities. KCCQ was significantly worse in COPD patients. The ADO and BODE indices were significantly different.

Conclusion

COPD is very common in unselected HF patients. It was often not diagnosed and many patients received treatment without being diagnosed with COPD. Presence of COPD worsens symptoms and negatively effects cardiac specific QOL.

     

Neonatal calves develop airflow limitation due to chronic hypobaric hypoxia

Neonates and infants presenting with pulmonary hypertension and chronic hypoxia often exhibit airway obstruction. To investigate this association, we utilized a system in which neonatal calves are exposed to chronic hypobaric hypoxia and develop severe pulmonary hypertension. For the present study, one of each pair of six age-matched pairs of neonatal calves was continuously exposed to hypobaric hypoxia at 4,500 m (CH); the other remained at 1,500 m. At 2 wk of age, mean pulmonary arterial pressure (MPAP), dynamic lung compliance (Cdyn), resistance (RL), and static respiratory system compliance (Crs) were measured at 4,500 m in both CH and control calves exposed acutely to hypoxia (C). These measurements were repeated after cumulative administrations of nebulized methacholine (MCh). Tissues were removed for histological examination and assessment of bronchial ring contractility to MCh and KCl. After 2 wk of hypobaric hypoxia, MPAP (C 35 +/- 1.7 vs. CH 120 +/- 7 mmHg, P less than 0.001) and RL (C 2.64 +/- 0.16 vs CH 4.99 +/- 0.47 cmH2O.l-1s, P less than 0.001) increased. Cdyn (C 0.100 +/- 0.01 vs. CH 0.082 +/- 0.007 l/cmH2O) and Crs (CH 0.46 +/- 0.003 vs. C 0.59 +/- 0.009 l/cmH2O) were not significantly different. Compared with airways of C calves, airways of CH animals did not exhibit in vivo or in vitro MCh hyperresponsiveness; however, in vitro contractility to KCl of airways from CH animals was significantly increased. Histologically, airways from the CH calves showed increases in airway fibrous tissue and smooth muscle.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of mild-to-moderate airflow limitation on exercise capacity

To determine the effect of mild-to-moderate airflow limitation on exercise tolerance and end-expiratory lung volume (EELV), we studied 9 control subjects with normal pulmonary function [forced expired volume in 1 s (FEV1) 105% pred; % of forced vital capacity expired in 1 s (FEV1/FVC%) 81] and 12 patients with mild-to-moderate airflow limitation (FEV1 72% pred; FEV1/FVC % 58) during progressive cycle ergometry. Maximal exercise capacity was reduced in patients [69% of pred maximal O2 uptake (VO2max)] compared with controls (104% pred VO2max, P less than 0.01); however, maximal expired minute ventilation-to-maximum voluntary ventilation ratio and maximal heart rate were not significantly different between controls and patients. Overall, there was a close relationship between VO2max and FEV1 (r2 = 0.62). Resting EELV was similar between controls and patients [53% of total lung capacity (TLC)], but at maximal exercise the controls decreased EELV to 45% of TLC (P less than 0.01), whereas the patients increased EELV to 58% of TLC (P less than 0.05). Overall, EELV was significantly correlated to both VO2max (r = -0.71, P less than 0.001) and FEV1 (r = -0.68, P less than 0.001). This relationship suggests a ventilatory influence on exercise capacity; however, the increased EELV and associated pleural pressures could influence cardiovascular function during exercise. We suggest that the increase in EELV should be considered a response reflective of the effect of airflow limitation on the ventilatory response to exercise.     

The natural history of chronic airflow obstruction.

A prospective epidemiological study of the early stages of the development of chronic obstructive pulmonary disease was performed on London working men. The findings showed that forced expiratory volume in one second (FEV1) falls gradually over a lifetime, but in most non-smokers and many smokers clinically significant airflow obstruction never develops. In susceptible people, however, smoking causes irreversible obstructive changes. If a susceptible smoker stops smoking he will not recover his lung function, but the average further rates of loss of FEV1 will revert to normal. Therefore, severe or fatal obstructive lung disease could be prevented by screening smokers'' lung function in early middle age if those with reduced function could be induced to stop smoking. Infective processes and chronic mucus hypersecretion do not cause chronic airflow obstruction to progress more rapidly. There are thus two largely unrelated disease processes, chronic airflow obstruction and the hypersecretory disorder (including infective processes).     

Relationship between the partial pressure of arterial oxygen and airflow limitation in children with cystic fibrosis.

To assess whether it would be possible to avoid repeated arterial blood sampling in children with cystic fibrosis, the relation between the forced expiratory flow at 25% to 75% of the vital capacity (FEF25%-75%) and the partial pressure of arterial oxygen (PaO2) was examined. The PaO2 and the logarithm of the FEF25%-75% (expressed as a percentage of that predicted) showed the strongest correlation (r = 0.89, p less than 0.001). Although this relation cannot be used when an accurate value for the PaO2 is required, it can sometimes be useful for determining the need for an arterial puncture.     

Response of pulmonary circulation to oral pirbuterol in chronic airflow obstruction.

The effects of the oral beta agonist pirbuterol on pulmonary haemodynamics and gas exchange were studied in nine patients with severe irreversible airflow obstruction and moderate arterial hypoxaemia. After administration of 15 mg pirbuterol pulmonary vascular resistance fell by 19% but cardiac output rose by 24%, so that pulmonary arterial pressure showed no significant change. Systemic arterial oxygen pressure fell by 7%, limiting the rise in oxygen delivery to 21%. All changes were significant at the 2% level. These results show that pirbuterol dilates the pulmonary bed at the cost of a slight worsening of gas exchange, which is compensated by an independent rise in blood flow.     

Combination bronchodilator therapy in the management of chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) represents a significant cause of global morbidity and mortality, with a substantial economic impact. Recent changes in the Global initiative for chronic Obstructive Lung Disease (GOLD) guidance refined the classification of patients for treatment using a combination of spirometry, assessment of symptoms, and/or frequency of exacerbations. The aim of treatment remains to reduce existing symptoms while decreasing the risk of future adverse health events. Long-acting bronchodilators are the mainstay of therapy due to their proven efficacy. GOLD guidelines recommend combining long-acting bronchodilators with differing mechanisms of action if the control of COPD is insufficient with monotherapy, and recent years have seen growing interest in the additional benefits that combination of long-acting muscarinic antagonists (LAMAs), typified by tiotropium, with long-acting β₂-agonists (LABAs), such as formoterol and salmeterol. Most studies have examined free combinations of currently available LAMAs and LABAs, broadly showing a benefit in terms of lung function and other patient-reported outcomes, although evidence is limited at present. Several once- or twice-daily fixed-dose LAMA/LABA combinations are under development, most involving newly developed monotherapy components. This review outlines the existing data for LAMA/LABA combinations in the treatment of COPD, summarizes the ongoing trials, and considers the evidence required to inform the role of LAMA/LABA combinations in treatment of this disease.     

Exercise performance following a carbohydrate load in chronic airflow obstruction

We evaluated the effects of a large (920 cal) liquid carbohydrate (CHO) load on the maximum exercise capacity of 18 patients with chronic airflow obstruction [forced expiratory volume at at 1 s (FEV1) = 1.27 +/- 0.48 liters; FEV1/forced vital capacity = 0.41 +/- 0.11]. Patients underwent duplicate incremental cycle ergometer exercise tests to a symptom-limited maximum following CHO and a liquid placebo in single-blind fashion. Expired gas measurements were obtained during each power output. In 12 patients arterial blood gases were measured, and in six patients venous blood was obtained for measurement of glucose, electrolytes, and osmolality. With CHO, the maximum power output decreased from 86 +/- 30 to 76 +/- 31 W (P less than 0.001), whereas the ventilation at exhaustion was nearly identical (47.6 +/- 13.2 and 46.8 +/- 12.5 l/min). Arterial partial pressure of CO2 (PaCO2) at exhaustion decreased (P less than 0.025), arterial partial pressure of O2 (PaO2) increased (P less than 0.01), and the ventilatory equivalent for CO2 (VE/VCO2) increased (P less than 0.005) with CHO. At equivalent power outputs, CHO resulted in significant increases in VE (P less than 0.001) and VCO2 (P less than 0.001); PaCO2 was unchanged, whereas PaO2 increased (P less than 0.01). CHO increased the serum glucose at rest and during exercise. No changes in serum osmolality or electrolytes occurred during exercise following CHO. After CHO loading, the majority of patients appeared to reach their limiting level of ventilation at a lower power output. In contrast, there was no significant difference in the mean maximum power output with CHO in six normal control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)     

Airway hysteresis in normal subjects and individuals with chronic airflow obstruction

Specific conductance (sGaw) was measured without prior pharmacological induction of bronchoconstriction before and 5-10 s after a total lung capacity (TLC) volume history in normal subjects and in individuals with chronic airflow obstruction (CAO); increased sGaw after inspiration to TLC was considered evidence of airway hysteresis. Lung elastic recoil [Pst(L)] was also measured before and after inspiration to TLC. In the normal subjects 1) prebronchodilator sGaw increased significantly, whereas Pst(L) decreased significantly after inspiration to TLC; 2) modulators of cyclooxygenase activity had no significant effects on sGaw responses to deep inspiration; and 3) airway hysteresis diminished after inhalation of atropine or metaproterenol. In the CAO group 1) prebronchodilator sGaw and Pst(L) decreased significantly after inspiration to TLC, and 2) bronchoconstriction after deep inspiration diminished after inhalation of atropine or metaproterenol. This study demonstrates that normal airways exhibit hysteresis even without alteration of resting airway tone and that airway hysteresis is impaired in CAO.     

The effect of nutrient limitation on styrene metabolism in Pseudomonas putida CA-3.

Styrene degradation in Pseudomonas putida CA-3 has previously been shown to be subject to catabolite repression in batch culture. We report here on the catabolite-repressing effects of succinate and glutamate and the effects of a limiting inorganic-nutrient concentration on the styrene degradation pathway of P. putida CA-3 in a chemostat culture at low growth rates (0.05 h-1). Oxidation of styrene and the presence of styrene oxide isomerase and phenylacetaldehyde dehydrogenase activities were used as a measure of the expression of the styrene degradation pathway. Both glutamate and succinate failed to repress the styrene degradation ability under growth conditions of carbon and energy limitation. Lower levels of enzyme activities of the styrene degradation pathway were seen in cells grown on styrene or phenylacetic acid (PAA) under conditions of both ammonia and sulfate limitation than were seen under carbon and energy limitation. Cells grown on PAA under continuous culture oxidize styrene and styrene oxide and possess styrene oxide isomerase and NAD(+)-dependent phenylacetaldehyde dehydrogenase activities. Catabolite repression of styrene metabolism was observed in cells grown on styrene or PAA in the presence of growth-saturating (nonlimiting) concentrations of succinate or glutamate under sulfate limitation.     

Mechanism of the postcoital contraceptive effect of LH-RH in the rat. I. Serum hormone levels during chronic LH-RH Administration.

The mechanism of the postcoital contraceptive effect of luteinizing hormone-releasing hormone (LH-RH) was studied in the rat. 200 mcg of LH-RH administered daily over Days 1-7 of pregnancy produced a dramatic inhibition of pregnancy. This inhibition was directly correlated with induced 'surges' in serum LH over Days 1-4. Serum follicle stimulating hormone and prolactin were, in general, reduced over this same time period. A 48-hour delay in the preimplantation (Day 3) 'surge' in serum estradiol accompanied by a significant (ps less than .05 and less than .01) reduction in serum progesterone on Days 3, 4, 6, and 7 was also observed. The delayed 'surge' in serum estradiol on Day 5 and reduction in serum progesterone was correlated with an increase in folliculogenesis and luteolysis of established corpora lutea, respectively. These data suggest that in the rat LH-RH induces a rise in serum LH which is luteolytic during pregnancy and delays the serum estradiol surge necessary for normal implantation.