General discussion
Future perspectives
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Summary
The aim of this thesis is to provide more insight in the occurrence of COPD and pulmonary function abnormalities using different definitions in patients with CHF. In addition, we aimed to determine under- and overdiagnosis of COPD, the necessity of performing serial PFTs to correctly diagnose COPD, and predictors of pulmonary function abnormalities using different definitions in patients with CHF. Finally, we aimed to evaluate the effect of inhaled bronchodilators on pulmonary function and dyspnea in patients with CHF.
In chapter 2 we determined the prevalence as well as over- and underdiagnosis of COPD according to the widely used GOLD criteria in 187 outpatients with stable non-congested CHF with LVSD. In addition, we investigated whether serial PFTs are necessary for the correct diagnosis of COPD in this group of patients by using initial as well as confirmatory spirometry three months after treatment with tiotropium in patients with newly diagnosed COPD. We found COPD to be a frequent co-morbidity in patients with CHF, occurring in approximately one-third of the patients. Importantly, it was often unrecognized (19%) or overdiagnosed (32%). Furthermore, we concluded that under stable and euvolemic conditions a confirmatory spirometry is unnecessary for the correct diagnosis of COPD, as it did not change a newly established diagnosis of COPD in the vast majority of patients with CHF.
In chapter 3 we determined the prevalence of COPD in 187 outpatients with stable non-congested CHF with LVSD according to two definitions of airflow obstruction: the LLN (ATS/ERS guidelines) versus the fixed ratio of FEV1/FVC < 0.70 (GOLD guidelines). We found that the exact definition of airflow obstruction alters COPD prevalence substantially; one fifth, rather than one third, of the patients with CHF had concomitant COPD using the LLN instead of the fixed ratio. Importantly, the LLN seemed to identify clinically more important COPD than the fixed ratio of 0.7; 38% of patients with GOLD-COPD who were potentially misclassified as having COPD (FEV1/FVC < 0.7 but > LLN) did not differ significantly from those without COPD in terms of respiratory symptoms and risk factors for COPD, whereas patients with LLN-COPD did.
In chapter 4 we investigated the occurrence of pulmonary function abnormalities in 164 outpatients with CHF with LVSD according to the LLN versus conventional cutoff values (i.e. FEV1/VC < LLN versus FEV1/FVC < 0.7 for airway obstruction, TLCOc < LLN versus < 80% predicted for diffusion impairment, and TLC < LLN versus < 80% predicted for restriction). We excluded patients with known pulmonary, pleural, neuromuscular, collagen vascular, or other diseases that could affect pulmonary function. Patients
with a BMI above 35 were excluded from the restriction prevalence analysis. Pulmonary function abnormalities, especially diffusion impairment and airway obstruction, were highly prevalent in patients with CHF, even in a stable and non-congested condition and even though we used the LLN to better account for age. However, prevalence rates varied significantly according to the definition used between 44% and 58% for diffusion impairment and between 26% and 37% for airway obstruction using the LLN versus conventional cutoff values, respectively. In contrast to previous reports, restriction was found to be infrequent in this population of less severe and mainly stable CHF patients without pulmonary congestion, irrespective of the definition used (7% versus 5%, respectively). The conventional cutoff values classified more patients as having diffusion impairment, airway obstruction, or a mixed category compared to the LLN and failed to identify correctly 34% of patients with normal lung function placing them falsely within a pulmonary dysfunction category. Using the conventional cutoff values instead of the LLN led to misclassification of 27% of the patients. In chapter 5 we assessed predictors of pulmonary function impairment in 164 outpatients with CHF with LVSD according to the LLN in comparison to conventional cutoff values. The same exclusion criteria as described in chapter 4 were applied. We found that the LLN criterion identified an extra independent predictor of diffusion impairment compared to the 80% predicted value; in addition to BMI, PY, and VA, female gender also turned out to be an independent predictor of diffusion impairment using the LLN. A smoking history of ≥ 10 PY was a significant predictor of diffusion impairment and airway obstruction using the LLN criterion, but not using the conventional cutoff values. However, lowering the cutoff points of conventional criteria to match the more stringent LLN and thus avoid overdiagnosis of diffusion impairment and airway obstruction in the elderly, produced similar results as the LLN. Lower lung volumes were found in patients with pulmonary congestion, cardiomegaly, and a history of CABG.
Finally, in chapter 6 we evaluated retrospectively the effect of inhaled bronchodilators (combined 400 μg salbutamol and 80 μg ipratropium bromide) on pulmonary function and dyspnea in 116 outpatients with CHF and LVSD. Patients with a history of COPD or asthma were excluded. The results of our study confirmed that inhaled broncho- dilators have the potential to improve pulmonary function in patients with CHF, especially in those with airway obstruction. Importantly, full reversal of airway obstruction was seen in approximately 40% of patients without a history of COPD or asthma who had pre-bronchodilator airway obstruction. Significant improvements in pulmonary function were noted in all spirometric indices except for FVC and inspiratory capacity (IC) in the entire study population. Significant BDR of FEV1 (> 200 mL and > 12% from the baseline value) was noted in 12%. Patients with both
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persisting and fully reversible airway obstruction had significant BDR of FEV1 more often than patients without airway obstruction (23%, 16%, and 2%, respectively). Improvement in dyspnea at rest after bronchodilation was, however, small and did not correlate to improvement in pulmonary function in this selected study population.
Conclusions
§ COPD is a frequent co-morbidity in patients with stable non-congested CHF with LVSD, but is often unrecognized or overdiagnosed.
§ Spirometry should be used under stable and euvolemic conditions to decrease the burden of undiagnosed or overdiagnosed COPD in patients with CHF. Under these conditions, a confirmatory spirometry is unnecessary, as it does not change a newly established diagnosis of COPD in the vast majority of patients with CHF. § The exact definition of airflow obstruction alters COPD prevalence substantially;
one fifth, rather than one third, of the patients with CHF have concomitant COPD using the LLN instead of the fixed ratio.
§ LLN may identify clinically more important COPD than the fixed ratio of 0.7 as patients who are potentially misclassified as having COPD, in contrast to patients with LLN-COPD, do not differ significantly from those without COPD in terms of respiratory symptoms and risk factors for COPD.
§ Pulmonary function abnormalities, especially diffusion impairment and airway obstruction, are highly prevalent in patients with CHF.
§ Conventional cutoff values classify more patients as having diffusion impairment, airway obstruction, or a mixed category compared to the LLN, leading to mis- classification of 27% of the patients.
§ The LLN identifies more predictors of diffusion impairment and airway obstruction compared to the conventional cutoff values. However, lowering the conventional cutoff points to match the more stringent LLN, produces similar results as the LLN. § Inhaled bronchodilators may have an additional role in the management of patients
with CHF because of their potential to improve pulmonary function, especially in those with airway obstruction. Improvement in dyspnea is, however, small and does not correlate to improvement in pulmonary function in this selected study population.