Different dyspnoea perception in COPD patients with frequent and infrequent exacerbations.

BACKGROUND: Some patients with COPD report frequent acute exacerbations (AECOPD) of the disease (FE), whereas others suffer them infrequently (IE). Because the current diagnosis of exacerbation relies on patient's perception of increased symptoms (mostly dyspnoea), we hypothesised that dyspnoea perception might be different in COPD patients with FE (≥2 exacerbations or 1 hospitalisation due to AECOPD in the previous year) or IE (≤1 exacerbation in the previous year), AECOPD being defined by the institution antibiotics and/or steroids treatment, or hospital admission. OBJECTIVE: To test the hypothesis that dyspnoea perception is increased in FE and/or decreased in IE with COPD. METHODS: We compared the perception of dyspnoea (Borg scale), mouth occlusion pressure 0.1 s after the onset of inspiration (P0.1) and ventilatory response to hypercapnia (ΔVE/ΔPETCO2) in 34 clinically stable COPD patients with FE (n=14) or IE (n=20), with similar age, gender, body mass index and degree of airflow limitation. As a reference, we studied a group of age-matched healthy volunteers (n=10) with normal spirometry. RESULTS: At rest, P0.1 was higher in FE than IE and controls (p<0.01). Compared with controls, the ventilatory response to hypercapnia was equally blunted both in FE and IE (p<0.001). Despite similar spirometry, during rebreathing peak Borg score and ΔBorg were higher (p<0.01) in FE and lower (p<0.01) in IE, than in controls. CONCLUSIONS: Dyspnoea perception during CO2 rebreathing is enhanced in FE and blunted in IE. These differences may contribute to the differential rate of reported exacerbations in FE and IE. TRIAL REGISTRATION NUMBER: NCT02113839.

Lung function abnormalities are highly frequent in patients with heart failure and preserved ejection fraction.

BACKGROUND: Heart failure with preserved ejection fraction (HFPEF) is the most prevalent form of heart failure in outpatients. Yet, the pathophysiology of this syndrome is unclear and pharmacological treatment does not improve prognosis. Because breathlessness during activities of daily living is the most frequent complaint of patients with HFPEF, we hypothesised that lung function may be often abnormal in these patients due to either a direct effect of HFPEF and/or shared risk factors. In this study we explore the frequency, type and severity of lung function abnormalities in HFPEF. METHODS: We measured forced spirometry, static lung volumes, pulmonary diffusing capacity (DL(CO)) and arterial blood gases in 69 outpatients with newly diagnosed symptomatic HFPEF. RESULTS: We found that 94% of the patients showed abnormalities in at least one of the lung function measurements obtained: spirometry was abnormal in 59%, DL(CO) in 83% and arterial hypoxaemia was present in 62%. Their severity varied between patients, they were more prevalent in patients with NYHA functional class III/IV, and most often they were undiagnosed and untreated. CONCLUSIONS: Lung function abnormalities are very frequent in HFPEF patients. A greater awareness among clinicians may contribute to improve their management and health status.

Hemodynamic and gas exchange effects of sildenafil in patients with chronic obstructive pulmonary disease and pulmonary hypertension.

RATIONALE: Sildenafil, a phosphodiesterase-5 inhibitor, could be useful for treating pulmonary hypertension (PH) in chronic obstructive pulmonary disease (COPD). However, vasodilators may inhibit hypoxic pulmonary vasoconstriction and impair gas exchange in this condition. OBJECTIVES: To assess the acute hemodynamic and gas exchange effects of sildenafil in patients with COPD-associated PH. METHODS: We conducted a randomized, dose comparison trial in 20 patients with COPD-associated PH. Eleven patients were assigned to 20 mg, and 9 patients to 40 mg, of sildenafil. Pulmonary hemodynamics and gas exchange, including ventilation-perfusion (V(A)/Q) relationships, were assessed at rest and during constant-work rate exercise, before and 1 hour after sildenafil administration. MEASUREMENTS AND MAIN RESULTS: Both sildenafil doses reduced the mean pulmonary arterial pressure (PAP) at rest and during exercise, without differences between them. Overall, PAP decreased -6 mm Hg (95% confidence interval [95% CI], -7 to -4) at rest and -11 mm Hg (95% CI, -14 to -8) during exercise. After sildenafil, Pa(O(2)) decreased -6 mm Hg (95% CI, -8 to -4) at rest because of increased perfusion in units with low V(A)/Q ratio, without differences between doses. No change in Pa(O(2)) (95% CI, -3 to 0.2 mm Hg) or V(A)/Q relationships occurred during exercise after sildenafil. Changes induced by sildenafil in Pa(O(2)) and V(A)/Q distributions at rest correlated with their respective values at baseline. CONCLUSIONS: In patients with COPD-associated PH, sildenafil improves pulmonary hemodynamics at rest and during exercise. This effect is accompanied by the inhibition of hypoxic vasoconstriction, which impairs arterial oxygenation at rest. The use of sildenafil in COPD should be done cautiously and under close monitoring of blood gases. Clinical trial registered with www.clinicaltrials.gov (NCT00491803).

Training-induced changes on quadriceps muscle oxygenation measured by near-infrared spectroscopy in healthy subjects and in chronic obstructive pulmonary disease patients.

AIM: We hypothesize that training-induced changes in muscle oxygen saturation (StO2 ) assessed by near-infrared spectroscopy (NIRS) during constant work rate cycling exercise (CWRE) may be a useful marker of the effects of training at 'vastus medialis' of the quadriceps in patients with chronic obstructive pulmonary disease (COPD). METHODS: Incremental exercise [peak oxygen uptake (VO2 )] and CWRE at 70% pretraining peak VO2 , before and after 8-w training, were done in 10 healthy age-matched subjects (H) [80% men, 65(11) years, FEV1 105(14)%] and 16 COPD patients [94% men, 70(5) years, FEV1 46(11) %] encompassing the entire spectrum of disease severity, recruited in the outpatient clinics. NIRS was used to assess StO2 in the 'vastus medialis' of the left quadriceps. RESULTS: Pretraining CWRE decreased StO2 (P<0·05) and generated marked StO2 rebound (P<0·001) after unloading in the two groups. After training, VO2 peak increased in H [253(204) ml min-1 ] (P<0·01) and in COPD [180(183) ml·min-1 ] (P = 0·01) and blood lactate fell [-4·4 (2·7) and -1·6(2·3) mmol·m-1 ] (P<0·05 each). Training generated a further fall in StO2 during CWRE [-10(12)% and -10(10)%, P<0·05] and increased StO2 rebound after unloading [8(7)% and 5(9)%, P<0·05] in both groups. CONCLUSION: Endurance training further decreased StO2 during CWRE, similarly in both groups, likely due to training-induced enhancement of muscle O2 transfer and utilization. Training-induced StO2 fall during CWRE may be useful individual marker for non-invasive assessment of enhanced muscle aerobic post-training function.

Automated Spirometry Quality Assurance: Supervised Learning From Multiple Experts.

Forced spirometry testing is gradually becoming available across different healthcare tiers including primary care. It has been demonstrated in earlier work that commercially available spirometers are not fully able to assure the quality of individual spirometry manoeuvres. Thus, a need to expand the availability of high-quality spirometry assessment beyond specialist pulmonary centres has arisen. In this paper, we propose a method to select and optimise a classifier using supervised learning techniques by learning from previously classified forced spirometry tests from a group of experts. Such a method is able to take into account the shape of the curve as an expert would during visual inspection. We evaluated the final classifier on a dataset put aside for evaluation yielding an area under the receiver operating characteristic curve of 0.88 and specificities of 0.91 and 0.86 for sensitivities of 0.60 and 0.82. Furthermore, other specificities and sensitivities along the receiver operating characteristic curve were close to the level of the experts when compared against each-other, and better than an earlier rules-based method assessed on the same dataset. We foresee key benefits in raising diagnostic quality, saving time, reducing cost, and also improving remote care and monitoring services for patients with chronic respiratory diseases in the future if a clinical decision support system with the encapsulated classifier is to be integrated into the work-flow of forced spirometry testing.

Pulmonary function predicts mortality and hospitalizations in outpatients with heart failure and preserved ejection fraction.

BACKGROUND: Heart failure with preserved ejection fraction (HFPEF) is the most frequent form of heart failure in ambulatory patients with new-onset symptoms. We previously showed that lung function abnormalities are highly prevalent in HFPEF patients. In this observational, longitudinal study, we tested the hypothesis that the presence of airflow limitation and/or arterial hypoxemia predicts mortality and/or cardiovascular hospitalizations during follow-up in HFPEF outpatients. MATERIALS AND METHODS: HFPEF was diagnosed following the international recommendations. Forced spirometry and arterial blood gases were measured at recruitment according to international recommendations. The primary endpoint of the study was all-cause mortality and the secondary one was any cardiovascular hospitalization. RESULTS: We included in the analysis all consecutive outpatients newly diagnosed of HFPEF in our clinic between April 2009 and January 2013 (n = 71). Patients were prospectively followed up for a mean of 4 years (range 10 months to 5.8 years). All-cause mortality was 18.3%. It was higher in patients with airflow limitation (30%) than those with normal spirometry (10%) or other spirometric defects (19%) (p = 0.036). The presence of arterial hypoxemia did not predict mortality (p = 0.179) but was significantly related to cardiovascular hospitalizations during follow-up (p = 0.038). CONCLUSIONS: The presence of airflow limitation or arterial hypoxemia identify a group of patients with HFPEF at higher risk of death or cardiovascular hospitalizations, respectively. Given that both airflow limitation and arterial hypoxemia are treatable, we propose that lung function should be routinely evaluated in the outpatient management of HFPEF patients.

Postural effects on pulmonary gas exchange abnormalities in severe obesity before and after bariatric surgery.

BACKGROUND: We hypothesized that in morbid obesity, pulmonary gas exchange abnormalities will worsen when supine and that bariatric surgery (BS) will mitigate this effect. METHODS: Gas exchange was investigated in 19 morbidly obese and 8 non-obese, age-matched control females, spontaneously breathing ambient air, both upright and supine, before and one year after BS. RESULTS: In control non-obese individuals, no postural changes in arterial blood gases (ABGs) were observed. While obese subjects had more altered PaO2, SaO2 and AaPO2 values than controls (P<0.05 each) when upright, the values unexpectedly remained unchanged when supine. This was also the case in the subset of 6 normoxemic obese but the remaining 13 hypoxemic individuals actually improved ABGs when supine: PaO2 (by +2.7±1.3 mmHg, P=0.06), SaO2 (by +1.5±0.6%), pH (by +0.01±0.01) and AaPO2 (by -3.4±1.4 mmHg); and cardiac output increased (by +0.4±0.2 L·min-1) (P<0.05 each). After BS, PaO2 (from 75.5±2.4 to 89.4±2.4 mmHg), AaPO2 (from 27.0±2.0 to 15.4±2.1 mmHg) (P<0.05 each), and pulmonary gas exchange were improved compared to before BS when upright, but ABGs worsened when supine (PaO2, by -4.6±1.7 mmHg; AaPO2, by +4.2±1.6 mmHg) (P<0.05 each). CONCLUSIONS: Before BS, ABGs are not altered in normoxemic obese subjects moving from upright to supine, even improving in those with hypoxemia when supine. After successful BS, pulmonary gas exchange improved when upright in all subjects but ABGs deteriorated when supine. However, the important clinical observation is the lack of gas exchange deterioration when supine, which may have implications for critical care and anesthesia settings.

Ventilation/Perfusion distribution abnormalities in morbidly obese subjects before and after bariatric surgery.

BACKGROUND: Obesity is a global and growing public health problem. Bariatric surgery (BS) is indicated in patients with morbid obesity. To our knowledge, the effects of morbid obesity and BS on ventilation/perfusion (V.a/Q.) ratio distributions using the multiple inert gas elimination technique have never before been explored. METHODS: We compared respiratory and inert gas (V.a/Q. ratio distributions) pulmonary gas exchange, breathing both ambient air and 100% oxygen, in 19 morbidly obese women (BMI, 45 kg/m2), both before and 1 year after BS, and in eight normal-weight, never smoker, age-matched, healthy women. RESULTS: Before BS, morbidly obese individuals had reduced arterial Po2 (76 ± 2 mm Hg) and an increased alveolar-arterial Po2 difference (27 ± 2 mm Hg) caused by small amounts of shunt (4.3% ± 1.1% of cardiac output), along with abnormally broadly unimodal blood flow dispersion (0.83 ± 0.06). During 100% oxygen breathing, shunt increased twofold in parallel with a reduction of blood flow to low V.a/Q. units, suggesting the development of reabsorption atelectasis without reversion of hypoxic pulmonary vasoconstriction. After BS, body weight was reduced significantly (BMI, 31 kg/m2), and pulmonary gas exchange abnormalities were decreased. CONCLUSIONS: Morbid obesity is associated with mild to moderate shunt and V.a/Q. imbalance. These abnormalities are reduced after BS.

Effects of nebulized N(G)-nitro-L-arginine methyl ester in patients with hepatopulmonary syndrome.

Enhanced pulmonary production of nitric oxide (NO) has been implicated in the pathogenesis of hepatopulmonary syndrome (HPS). NO inhibition with N(G)-nitro-L-arginine methyl ester (L-NAME) in both animals and humans with HPS has improved arterial hypoxemia. We assessed the role of enhanced NO production in the pathobiology of arterial deoxygenation in HPS and the potential therapeutic efficacy of selective pulmonary NO inhibition. We investigated the effects of nebulized L-NAME (162.0 mg) at 30 and 120 minutes on all intrapulmonary and extrapulmonary factors governing pulmonary gas exchange in 10 patients with HPS (60 +/- 7 [SD] yr; alveolar-arterial oxygen gradient, range 19-76 mm Hg; arterial oxygen tension, range 37-89 mm Hg). Nebulized L-NAME maximally decreased exhaled NO (by -55%; P < .001), mixed venous nitrite/nitrate (by -12%; P = .02), and cardiac output (by -11%; P = .002) while increased systemic vascular resistance (by 11%; P = .008) and pulmonary vascular resistance (by 25%; P = .03). In contrast, ventilation-perfusion mismatching, intrapulmonary shunt and, in turn, arterial deoxygenation remained unchanged. In conclusion, gas exchange disturbances in HPS may be related to pulmonary vascular remodeling rather than to an ongoing vasodilator effect of enhanced NO production.