Palliation of Dyspnea With Mouthpiece Ventilation in Patients With Chronic Obstructive Pulmonary Disease: A Pilot Feasibility Study.

Background: Mouthpiece ventilation (MPV) reduces hypoventilation, but its efficacy in relieving dyspnea in patients with acute chronic obstructive pulmonary disease exacerbation (AECOPD) is unclear. Objective: To assess the feasibility of MPV in relieving dyspnea among patients with AECOPD. Methods: In this prospective single-arm pilot study, the change in dyspnea on numeric rating scale (NRS) after using MPV and side effects of the treatment were studied in 18 patients with AECOPD. Results: The median decrease in dyspnea was 1.5 (95% confidence interval = 0.0-2.5, p = 0.006) on NRS after the intervention lasting a median of 16.9 minutes. Of the patients, 61% found MPV beneficial. The use of MPV did not increase the sense of anxiety or pain. Conclusions: MPV is feasible and may relieve dyspnea in patients with AECOPD, but the intervention needs further evaluation. clinicaltrials.gov study number: NCT03025425.

Specialist Palliative Care Consultation for Patients with Nonmalignant Pulmonary Diseases: A Retrospective Study.

Background: Few patients with chronic nonmalignant pulmonary diseases receive specialist palliative care consultation, despite their high symptom burden in end of life. Objectives: To study palliative care decision making, survival, and hospital resource usage in patients with nonmalignant pulmonary diseases with or without a specialist palliative care consultation. Methods: A retrospective chart review of all patients with a chronic nonmalignant pulmonary disease and a palliative care decision (palliative goal of therapy), who were treated in Tampere University Hospital, Finland, between January 1, 2018 and December 31, 2020. Results: A total of 107 patients were included in the study, 62 (58%) had chronic obstructive pulmonary disease (COPD), and 43 (40%) interstitial lung disease (ILD). Median survival after palliative care decision was shorter in patients with ILD than in patients with COPD (59 vs. 213 days, p = 0.004). Involvement of a palliative care specialist in the decision making was not associated with the survival. Patients with COPD who received palliative care consultation visited less often emergency room (73% vs. 100%, p = 0.019) and spent fewer days in the hospital (7 vs. 18 days, p = 0.007) during the last year of life. When a palliative care specialist attended the decision making, the presence and opinions of the patients were recorded more often, and the patients were more frequently referred to a palliative care pathway. Conclusions: Specialist palliative care consultation seems to enable better end-of-life care and supports shared decision making for patients with nonmalignant pulmonary diseases. Therefore, palliative care consultations should be utilized in nonmalignant pulmonary diseases preferably before the last days of life.

Assessing Symptom Burden and Depression in Subjects With Chronic Respiratory Insufficiency.

Objectives: Patients with chronic respiratory insufficiency suffer from advanced disease, but their overall symptom burden is poorly described. We evaluated the symptoms and screening of depression in subjects with chronic respiratory insufficiency by using the Edmonton symptom assessment system (ESAS). Methods: In this retrospective study, 226 subjects with chronic respiratory insufficiency answered the ESAS questionnaire measuring symptoms on a scale from 0 (no symptoms) to 10 (worst possible symptom), and the depression scale (DEPS) questionnaire, in which the cut-off point for depressive symptoms is 9. Results: The most severe symptoms measured with ESAS (median [interquartile range]) were shortness of breath 4.0 (1.0-7.0), dry mouth 3.0 (1.0-7.0), tiredness 3.0 (1.0-6.0), and pain on movement 3.0 (0.0-6.0). Subjects with a chronic obstructive pulmonary disease as a cause for chronic respiratory insufficiency had significantly higher scores for shortness of breath, dry mouth, and loss of appetite compared to others. Subjects with DEPS ≥9 reported significantly higher symptom scores in all ESAS categories than subjects with DEPS <9. The area under the receiver operating characteristic curve for ESAS depression score predicting DEPS ≥9 was 0.840 (P < .001). If the ESAS depression score was 0, there was an 89% probability of the DEPS being <9, and if the ESAS depression score was ≥4, there was an 89% probability of the DEPS being ≥9. The relation between ESAS depression score and DEPS was independent of subjects' characteristics and other ESAS items. Conclusions: Subjects with chronic respiratory insufficiency suffer from a high symptom burden due to their advanced disease. The severity of symptoms increases with depression and 4 or more points in the depression question of ESAS should lead to a closer diagnostic evaluation of depression. Symptom-centered palliative care including psychosocial aspects should be early integrated into the treatment of respiratory insufficiency.

Dyspnea on Exercise Is Associated with Overall Symptom Burden in Patients with Chronic Respiratory Insufficiency.

Background: Patients with chronic respiratory insufficiency suffer from many symptoms together with dyspnea. Objective: We evaluated the association of dyspnea on exercise with other symptoms in patients with chronic respiratory insufficiency due to chronic obstructive pulmonary disease or interstitial lung disease. Design: This retrospective study included 101 patients in Tampere University Hospital, Finland. Dyspnea on exercise was assessed with modified Medical Research Council (mMRC) dyspnea questionnaire, and other symptoms were assessed with Edmonton Symptom Assessment System (ESAS) and Depression Scale (DEPS). The study was approved by Regional Ethics Committee of Tampere University Hospital, Finland (approval code R15180/December 1, 2015). Results: Patients with mMRC 4 (most severe dyspnea) compared with those with mMRC 0-3 reported higher symptom scores on ESAS in shortness of breath (median 8.0 [IQR 6.0-9.0] vs. 4.0 [2.0-6.0], p < 0.001), dry mouth (7.0 [4.0-8.0] vs. 3.0 [1.0-6.0], p < 0.001), tiredness (6.0 [3.0-7.0] vs. 3.0 [1.0-5.0], p < 0.001), loss of appetite (3.0 [0.0-6.0] vs. 1.0 [0.0-3.0], p = 0.001), insomnia (3.0 [1.0-7.0] vs. 2.0 [0.0-3.0], p = 0.027), anxiety (3.0 [0.0-5.5] vs. 1.0 [0.0-3.0], p = 0.007), and nausea (0.0 [0.0-2.0] vs. 0.0 [0.0-0.3], p = 0.027). Patients with mMRC 4 were more likely to reach the DEPS threshold for depression than those scoring mMRC 0-3 (42.1% vs. 20.8%, p = 0.028). Conclusions: Patients with chronic respiratory insufficiency need comprehensive symptom screening with relevant treatment, as they suffer from broad symptom burden worsening with increased dyspnea on exercise.

Survival and end-of-life aspects among subjects on long-term noninvasive ventilation.

BACKGROUND: The need for noninvasive ventilation (NIV) is commonly considered a predictor of poor survival, but life expectancy may vary depending on the underlying disease. We studied the factors associated with decreased survival and end-of-life characteristics in an unselected population of subjects starting NIV. METHODS: We conducted a retrospective study including 205 subjects initiating NIV from 1/1/2012-31/12/2015 who were followed up until 31/12/2017. RESULTS: The median survival time was shorter in subjects needing help with activities of daily living than in independent subjects (hazard ratio (HR) for death 1.7, 95% CI 1.2-2.6, P = 0.008) and was also shorter in subjects on long-term oxygen therapy (LTOT) than in those not on LTOT (HR for death 2.8, 95% CI 1.9-4.3, P < 0.001). There was marked difference in survival according to the disease necessitating NIV, and subjects with amyotrophic lateral sclerosis or interstitial lung disease seemed to have the shortest survival. The two most common diseases resulting in the need for NIV were chronic obstructive pulmonary disease (COPD) and obesity hypoventilation syndrome (OHS). The median survival time was 4.4 years in COPD subjects, but the median survival time was not reached in subjects with OHS (HR for death COPD vs. OHS: 3.2, 95% CI 1.9-5.5, P < 0.001). Most of the deceased subjects (55.6%) died in the hospital, while only 20.0% died at home. The last hospitalization admission leading to death occurred through the emergency room in 44.4% of the subjects. CONCLUSIONS: Survival among subjects starting NIV in this real-life study varied greatly depending on the disease and degree of functional impairment. Subjects frequently died in the hospital after admission through the emergency department. A comprehensive treatment approach with timely advance care planning is therefore needed, especially for those needing help with activities of daily living and those with both NIV and LTOT.

Mouthpiece ventilation in the management of dyspnea: A single-arm pilot study.

BACKGROUND: Noninvasive ventilation may relieve dyspnea in advanced diseases, but noninvasive ventilation through mouthpiece has not been tested in palliative care. AIM: To assess the feasibility of mouthpiece ventilation in relieving dyspnea among patients with advanced disease. DESIGN: In this prospective single-arm pilot study, the change in dyspnea by mouthpiece ventilation was measured with numeric rating scale (0-10) and 100-mm visual analogue scale. Overall, benefit and adverse events of the therapy were also assessed. SETTING/PARTICIPANTS: Twenty-two patients with an advanced disease and dyspnea from the Tampere University Hospital or Pirkanmaa Hospice were treated with mouthpiece ventilation. The patients used mouthpiece ventilation as long as they preferred, but for a minimum of 5 min. RESULTS: After the treatment period lasting a median of 13.5 min, mean decrease in dyspnea was -1.1 (95 % confidence interval = -2.2 to -0.1, p = 0.034) on numeric rating scale and -11.8 mm (95 % confidence interval = -19.9 to -3.7, p = 0.006) on visual analogue scale. Nonetheless, there was a high variability in this effect between individual patients. About half of the patients found mouthpiece ventilation beneficial. No serious adverse events occurred, but dry mouth was the most common adverse event. Anxiety did not increase with mouthpiece ventilation. CONCLUSION: Mouthpiece ventilation is feasible and may relieve dyspnea in some patients with an advanced disease. Further studies are needed, and these might concentrate on stable patients in early palliative care. Before initiation, this study was registered at clinicaltrials.gov (study no. NCT03012737).

Predictors of Impaired Survival in Subjects With Long-Term Oxygen Therapy.

BACKGROUND: The need for long-term oxygen therapy (LTOT) is usually a sign of advanced disease, which could trigger advance care planning. However, LTOT is used in patients with different characteristics and multiple diagnoses beyond COPD. We studied the factors associated with survival in an unselected sample of subjects who started LTOT. METHODS: We conducted a retrospective study that included 195 subjects for whom LTOT was initiated in Tampere University Hospital from January 1, 2012, to December 31, 2015, and followed up until December 31, 2017. RESULTS: The most frequent diseases that caused the need for LTOT were COPD and interstitial lung diseases. Most of the subjects (69%) died during the study period; the median survival time was 2.2 y. The subjects with interstitial lung disease as a primary disease for LTOT had a shorter survival time (median 0.9 y) compared with those with COPD (median 2.4 y, P < .001). Survival was shorter in the subjects ages >75 y (median 1.4 y) compared with those who were ages ≤75 y (median 2.8 y, P = .001) and also in those who required help with daily activities (median 1.2 y) compared with those who did not (median 3.3 y, P < .001). In multivariate analysis, a diagnosis of interstitial lung disease (hazard ratio 2.1, 95% CI 1.4-3.2), Charlson comorbidity index (hazard ratio 1.26, 95% Cl 1.11-1.43), and required help in activities of daily living (hazard ratio 2.1, 95% CI 1.4-3.1) were associated with impaired survival. CONCLUSIONS: The survival of the subjects who started LTOT varied greatly. The subjects with interstitial lung disease and those who required assistance with activities of daily living were at risk of dying in ∼1 y, which suggested that advance care planning should be directed especially to these patients.

Implementation of a depression screening protocol among respiratory insufficiency patients.

INTRODUCTION: Unnoticed and untreated depression is prevalent among patients with chronic respiratory insufficiency. Comorbid depression causes suffering and worsens patients' outcomes. OBJECTIVES: The objective of this evaluation was to assess preliminary outcomes of a depression screening protocol among chronic respiratory insufficiency patients at a tertiary care pulmonary outpatient clinic. METHODS: In the depression screening protocol, the patients filled the Depression Scale (DEPS) questionnaire. Patients whose scores suggested depression were offered the opportunity of a further evaluation of mood at a psychiatric outpatient clinic. The outcomes of the protocol were evaluated retrospectively from the patient records. RESULTS: During the period of evaluation, 238 patients visited the outpatient clinic. DEPS was administered to 176 patients (74%), of whom 60 (34%) scored ≥9 (out of 30), thus exceeding the cut-off for referral. However, only 13 patients were referred, as the remainder declined the referral. Finally, seven patients were evaluated at the psychiatric clinic, and they all were deemed depressive. Symptoms of depression were most prevalent among patients with a long smoking history, refractory dyspnoea and a history of depression. CONCLUSION: Depression screening was positive in a third of the patients. The depression screening protocol improved the detection of depression symptoms, but the effects on the patients' treatment and clinical course were small. Rather than referring patients to a psychiatric unit, the evaluation and management of depression should be undertaken at the pulmonary unit.

Adipokines NUCB2/nesfatin-1 and visfatin as novel inflammatory factors in chronic obstructive pulmonary disease.

COPD (chronic obstructive pulmonary disease) is a common lung disease characterized by airflow limitation and systemic inflammation. Recently, adipose tissue mediated inflammation has gathered increasing interest in the pathogenesis of the disease. In this study, we investigated the role of novel adipocytokines nesfatin-1 and visfatin in COPD by measuring if they are associated with the inflammatory activity, lung function, or symptoms. Plasma levels of NUCB2/nesfatin-1 and visfatin were measured together with IL-6, IL-8, TNF- α , and MMP-9, lung function, exhaled nitric oxide, and symptoms in 43 male patients with emphysematous COPD. The measurements were repeated in a subgroup of the patients after four weeks' treatment with inhaled fluticasone. Both visfatin and NUCB2/nesfatin-1 correlated positively with plasma levels of IL-6 (r = 0.341, P = 0.027 and rho = 0.401, P = 0.008, resp.) and TNF- α (r = 0.305, P = 0.052 and rho = 0.329, P = 0.033, resp.) and NUCB2/nesfatin-1 also with IL-8 (rho = 0.321, P = 0.036) in patients with COPD. Further, the plasma levels of visfatin correlated negatively with pulmonary diffusing capacity (r = -0.369, P = 0.016). Neither of the adipokines was affected by fluticasone treatment and they were not related to steroid-responsiveness. The present results introduce adipocytokines NUCB2/nesfatin-1 and visfatin as novel factors associated with systemic inflammation in COPD and suggest that visfatin may mediate impaired pulmonary diffusing capacity.

Adiponectin is associated with dynamic hyperinflation and a favourable response to inhaled glucocorticoids in patients with COPD.

OBJECTIVES: Adipokines are protein mediators first described as products of adipose tissue regulating energy metabolism and appetite. Recently, adipokines have also been found to modulate inflammation and smooth muscle cell responses. Therefore we investigated the association of two adipokines, adiponectin and leptin, with the degree of emphysema, pulmonary function, symptoms and glucocorticoid responsiveness in patients with COPD. METHODS: Plasma adiponectin and leptin levels, spirometry, body plethysmography and symptoms were measured in 43 male COPD patients with smoking history ≥ 20 pack-years, post bronchodilator FEV1/FVC < 0.7 and pulmonary emphysema on HRCT. The measurements were repeated in a subgroup of patients after 4 weeks' treatment with inhaled fluticasone. RESULTS: In patients with COPD, plasma adiponectin levels correlated positively with airway resistance (Raw) (r = 0.362, p = 0.019) and functional residual capacity (FRC) (r = 0.355, p = 0.046). Furthermore, the baseline adiponectin concentration correlated negatively with the fluticasone induced changes in St George's Respiratory questionnaire (SGRQ) symptom score (r = -0.413, p = 0.040) and in FRC % pred (r = -0.428, p = 0.003), i.e. a higher baseline plasma adiponectin level was associated with more pronounced alleviation of symptoms and dynamic hyperinflation. Plasma leptin levels were not related to the measures of lung function, symptoms or glucocorticoid responsiveness. CONCLUSIONS: Plasma adiponectin levels were associated with peripheral airway obstruction and dynamic hyperinflation in patients with COPD. A higher adiponectin level predicted more favourable relief of symptoms and hyperinflation during glucocorticoid treatment. Adiponectin may have a role in the COPD pathogenesis; it may also be a biomarker of disease severity and treatment responses in this disease.

Adipokine adipsin is associated with the degree of lung fibrosis in asbestos-exposed workers.

OBJECTIVES: Asbestos-exposure causes an inflammatory response driven by alveolar macrophages that can lead to pulmonary fibrosis. In addition to classical inflammatory cytokines, macrophages produce adipokines which regulate the inflammatory response. We studied if adipokines are related to the degree of parenchymal fibrosis, impaired lung function and inflammation in asbestos-exposed subjects. METHODS: Eighty-five males with moderate to heavy occupational exposure to asbestos and unexposed controls were studied. We measured plasma levels of adipokines adiponectin, adipsin, leptin and resistin, IL-6, IL-8, erythrocyte sedimentation rate (ERS), spirometry and D(L,CO). Degree of interstitial lung fibrosis (septal thickening, subpleural lines, parenchymal bands or honeycombing) was scored in classes 0-5 according to a validated scoring system. The subjects were divided into three groups: normal parenchymal finding (fibrosis class 0), borderline changes (classes 0.5-1.5) and fibrosis (i.e. asbestosis; classes 2-5). RESULTS: Adipsin correlated positively with parenchymal fibrosis (rho=0.412, p<0.001) and there was a linear increasing trend of mean plasma adipsin levels among the three groups of asbestos-exposed subjects (from normal parenchymal finding to borderline changes and to fibrosis) (p<0.0001). Accordingly, plasma adipsin levels correlated positively with the extent of pleural plaques (r=0.245, p=0.043), and negatively with D(L,CO) (r=-0.246, p=0.023). Also, a positive correlation was found between adipsin and inflammatory markers ESR (r=0.315, p=0.008) and IL-6 (r=0.256, p=0.018). CONCLUSIONS: Adipsin was associated with the degree of parenchymal fibrosis, impairment of pulmonary diffusing capacity and with inflammatory activity in asbestos-exposed subjects suggesting that adipsin may have a role in the pathogenesis or as a biomarker in asbestos-induced lung disease.

Adipokine resistin predicts anti-inflammatory effect of glucocorticoids in asthma.

BACKGROUND: Adipokines are protein mediators secreted by adipose tissue. Recently, adipokines have also been involved in the regulation of inflammation and allergic responses, and suggested to affect the risk of asthma especially in obese female patients. We assessed if adipokines predict responsiveness to glucocorticoids and if plasma adipokine levels are associated with lung function or inflammatory activity also in non-obese (body mass index (BMI) ≤ 30 kg/m2) women with newly-diagnosed steroid-naïve asthma. METHODS: Lung function, exhaled NO, plasma levels of adipokines leptin, resistin, adiponectin and adipsin, and inflammatory markers were measured in 35 steroid-naïve female asthmatics and in healthy controls. The measurements were repeated in a subgroup of asthmatics after 8 weeks of treatment with inhaled fluticasone. Adipokine concentrations in plasma were adjusted for BMI. RESULTS: High baseline resistin concentrations were associated with a more pronounced decrease in serum levels of eosinophil cationic protein (ECP) (r = -0.745, p = 0.013), eosinophil protein X (EPX) (r = -0.733, p = 0.016) and myeloperoxidase (MPO) (r = -0.721, p = 0.019) during fluticasone treatment. In asthmatics, leptin correlated positively with asthma symptom score and negatively with lung function. However, no significant differences in plasma adipokine levels between non-obese asthmatics and healthy controls were found. The effects of resistin were also investigated in human macrophages in cell culture. Interestingly, resistin increased the production of proinflammatory factors IL-6 and TNF-α and that was inhibited by fluticasone. CONCLUSIONS: High resistin levels predicted favourable anti-inflammatory effect of inhaled glucocorticoids suggesting that resistin may be a marker of steroid-sensitive phenotype in asthma. High leptin levels were associated with a more severe disease suggesting that the link between leptin and asthma is not restricted to obesity.