Development and validation of a prediction index for recent mortality in advanced COPD patients

The primary barrier to initiating palliative care for advanced COPD patients is the unpredictable course of the disease. We enroll 752 COPD patients into the study and validate the prediction tools for 1-year mortality using the current guidelines for palliative care. We also develop a composite prediction index for 1-year mortality and validate it in another cohort of 342 patients. Using the current prognostic models for recent mortality in palliative care, the best area under the curve (AUC) for predicting mortality is 0.68. Using the Modified Medical Research Council dyspnea score and oxygen saturation to define the combined dyspnea and oxygenation (DO) index, we find that the AUC of the DO index is 0.84 for predicting mortality in the validated cohort. Predictions of 1-year mortality based on the current palliative care guideline for COPD patients are poor. The DO index exhibits better predictive ability than other models in the study.

Evaluation of the Clinical Effectiveness of the Salmeterol/Fluticasone Fixed-Dose Combination Delivered via the Elpenhaler® Device in Greek Patients with Chronic Obstructive Pulmonary Disease and Comorbidities: The AEOLOS Study

Background: Chronic Obstructive Pulmonary Disease (COPD) is an inflammatory lung disease characterized by airflow limitation that is not completely reversible. The fixed-dose combination of salmeterol and fluticasone propionate (SFC) has been approved as a treatment for COPD patients with a history of recurrent exacerbations and significant symptoms despite regular bronchodilator therapy. In the present study, we evaluated the change in FEV1, mMRC dyspnea score and satisfaction in COPD patients with at least one comorbidity versus those without comorbidities treated with a fixed-dose SFC via the Elpenhaler® device for 12 months. Methods: A 12-month multicenter prospective, observational study (NCT02978703) was designed. Data were collected during the enrollment visit (V0) and six (V1) and twelve months (V2) after the initiation of treatment with Elpenhaler® SFC. The evaluation of the efficacy of the fixed-dose SFC was performed by assessing the change in lung function and dyspnea as expressed by FEV1 and the mMRC dyspnea scale score in COPD patients with and without comorbidities. Results: In total 1016 patients were enrolled, following usual daily clinical practice. A statistically significant improvement was observed in FEV1 in the total study population between visits V0, V1 and V2, with a change from the baseline at V1 0.15 ± 0.22 L and at V2 0.21 ± 0.25 L (p < 0.0001 for both comparisons). This improvement was exhibited regardless of the COPD severity at the baseline, being more noticeable in GOLD 2020 groups B and C. Similarly, a significant improvement was observed in mMRC dyspnea scale values between successive visits (p < 0.0001). In patients without comorbidities, there was a significant improvement in FEV1 of 0.19 ± 0.24 L at V1 and 0.28 ± 0.27 L at V2 (p < 0.0001 for both comparisons), as well as in the mMRC dyspnea score (p < 0.0001). In patients with at least one comorbidity, a corresponding but smaller improvement in FEV1 was observed (0.11 ± 0.34 L at V1 and 0.20 ± 0.42 L at V2; p < 0.0001 for both comparisons and in the mMRC score (p < 0.0001). In the multiple linear regression analysis BMI, GOLD 2020 groups, mMRC and the presence of comorbidities at the baseline were significant factors for the change of FEV1 between V0 and V2. Conclusions: COPD patients treated for twelve months with SFC via the Elpenhaler® device showed significant improvement in lung function and dyspnea at 6 and 12 months, irrespective of the presence of comorbidities.

Peripheral blood microbial signatures in current and former smokers

The human microbiome has a role in the development of multiple diseases. Individual microbiome profiles are highly personalized, though many species are shared. Understanding the relationship between the human microbiome and disease may inform future individualized treatments. We hypothesize the blood microbiome signature may be a surrogate for some lung microbial characteristics. We sought associations between the blood microbiome signature and lung-relevant host factors. Based on reads not mapped to the human genome, we detected microbial nucleic acids through secondary use of peripheral blood RNA-sequencing from 2,590 current and former smokers with and without chronic obstructive pulmonary disease (COPD) from the COPDGene study. We used the Genome Analysis Toolkit (GATK) microbial pipeline PathSeq to infer microbial profiles. We tested associations between the inferred profiles and lung disease relevant phenotypes and examined links to host gene expression pathways. We replicated our analyses using a second independent set of blood RNA-seq data from 1,065 COPDGene study subjects and performed a meta-analysis across the two studies. The four phyla with highest abundance across all subjects were Proteobacteria, Actinobacteria, Firmicutes and Bacteroidetes. In our meta-analysis, we observed associations (q-value < 0.05) between Acinetobacter, Serratia, Streptococcus and Bacillus inferred abundances and Modified Medical Research Council (mMRC) dyspnea score. Current smoking status was associated (q < 0.05) with Acinetobacter, Serratia and Cutibacterium abundance. All 12 taxa investigated were associated with at least one white blood cell distribution variable. Abundance for nine of the 12 taxa was associated with sex, and seven of the 12 taxa were associated with race. Host-microbiome interaction analysis revealed clustering of genera associated with mMRC dyspnea score and smoking status, through shared links to several host pathways. This study is the first to identify a bacterial microbiome signature in the peripheral blood of current and former smokers. Understanding the relationships between systemic microbial signatures and lung-related phenotypes may inform novel interventions and aid understanding of the systemic effects of smoking.

The Deteriorating Patient: Therapies Including Lung Transplantation

In this review paper, we discuss the characteristics that define severe bronchiectasis and which may lead to deterioration of noncystic fibrosis bronchiectasis. These characteristics were used to establish the current severity scores: bronchiectasis severity index (BSI), FACED, and E-FACED (exacerbation frequency, forced expiratory volume in 1 second, age, colonization, extension and dyspnea score). They can be used to predict mortality, exacerbation rate, hospital admission, and quality of life. Furthermore, there are different treatable traits that contribute to severe bronchiectasis and clinical deterioration. When present, they can be a target of the treatment to stabilize bronchiectasis.One of the first steps in treatment management of bronchiectasis is evaluation of compliance to already prescribed therapy. Several factors can contribute to treatment adherence, but to date no real interventions have been published to ameliorate this phenomenon. In the second step, treatment in deteriorating patients with bronchiectasis should be guided by the predominant symptoms, for example, cough, sputum, difficulty expectoration, exacerbation rate, or physical impairment. In the third step, we evaluate treatable traits that could influence disease severity in the deteriorating patient. Finally, in patients who are difficult to treat despite maximum medical treatment, eligibility for surgery (when disease is localized), should be considered. In case of end-stage disease, the evaluation for lung transplantation should be performed. Noninvasive ventilation can serve as a bridge to lung transplantation in patients with respiratory failure.

The Efficacy of High-flow Oxygen Versus Conventional Oxygen for Asthma Control: A Meta-analysis of Randomized Controlled Studies

Introduction: The efficacy of high-flow oxygen versus conventional oxygen therapy for asthma control remains controversial. We conduct a systematic review and meta-analysis to explore the influence of high-flow oxygen versus conventional oxygen therapy on asthma control. Methods: We have searched PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases through May 2021 for randomized controlled trials (RCTs) assessing the efficacy of high-flow oxygen versus conventional oxygen therapy for asthma control. This meta-analysis is performed using the random-effect model.Results: Four RCTs are included in the meta-analysis. Overall, compared with conventional oxygen therapy for asthma, high-flow oxygen is associated with significantly lower dyspnea score (SMD=-0.63; 95% CI=-1.08 to -0.17; P=0.008), but reveals no remarkable influence on PaCO2 (SMD=0.28; 95% CI=-0.22 to 0.77; P=0.28), PaO2 (SMD=0.44; 95% CI=-1.34 to 2.22; P=0.63), intubation (OR=1.09; 95% CI=0.15 to 8.21; P=0.93) or hospital length of stay (SMD=-0.07; 95% CI=-0.41 to 0.27; P=0.67). Conclusions: High-flow oxygen may benefit to reduce dyspnea score than conventional oxygen therapy for asthma.

Triple versus LAMA/LABA combination therapy for patients with COPD: a systematic review and meta-analysis

Background Recently, the addition of inhaled corticosteroid (ICS) to long-acting muscarinic antagonist (LAMA) and long-acting beta-agonist (LABA) combination therapy has been recommended for patients with COPD who have severe symptoms and a history of exacerbations because it reduces the exacerbations. In addition, a reducing effect on mortality has been shown by this treatment. However, the evidence is mainly based on one large randomized controlled trial IMPACT study, and it remains unclear whether the ICS add-on treatment is beneficial or not. Recently, a large new ETHOS trial has been performed to clarify the ICS add-on effects. Therefore, we conducted a systematic review and meta-analysis to evaluate the efficacy and safety including ETHOS trial. Methods We searched relevant randomized control trials (RCTs) and analyzed the exacerbations, quality of life (QOL), dyspnea symptom, lung function and adverse events including pneumonia and mortality, as the outcomes of interest. Results We identified a total of 6 RCTs in ICS add-on protocol (N = 13,579). ICS/LAMA/LABA treatment (triple therapy) significantly decreased the incidence of exacerbations (rate ratio 0.73, 95% CI 0.64–0.83) and improved the QOL score and trough FEV1 compared to LAMA/LABA. In addition, triple therapy significantly improved the dyspnea score (mean difference 0.33, 95% CI 0.18–0.48) and mortality (odds ratio 0.66, 95% CI 0.50–0.87). However, triple therapy showed a significantly higher incidence of pneumonia (odds ratio 1.52, 95% CI 1.16–2.00). In the ICS-withdrawal protocol including 2 RCTs, triple therapy also showed a significantly better QOL score and higher trough FEV1 than LAMA/LABA. Concerning the trough FEV1, QOL score and dyspnea score in both protocols, the differences were less than the minimal clinically important difference. Conclusion Triple therapy causes a higher incidence of pneumonia but is a more preferable treatment than LAMA/LABA due to the lower incidence of exacerbations, higher trough FEV1 and better QOL score. In addition, triple therapy is also superior to LABA/LAMA due to the lower mortality and better dyspnea score. However, these results should be only applied to patients with symptomatic moderate to severe COPD and a history of exacerbations. Clinical Trial Registration: PROSPERO; CRD42020191978.

Comparison of high-flow nasal oxygen cannula therapy versus a standard oxygen face mask in patients with hypostatic pneumonia

Objective We assessed the clinical effects of high-flow nasal cannula (HFNC) oxygen therapy and a standard oxygen atomizer mask on the respiratory tract in patients with hypostatic pneumonia. Methods We included patients with hypostatic pneumonia in this retrospective cohort study. Patients were provided continuous airway humidification by continuous oxygen atomization using either an HFNC or standard oxygen mask. Arterial blood gas analysis, the dyspnea score, inflammatory-related parameters, and adverse events of patients in the two groups were compared. Results Fifty-five patients had HFNC delivery and 57 had a standard oxygen atomizer mask. After 7 days of treatment, patients in the HFNC group had a higher partial pressure of arterial blood oxygen/fraction of inspired oxygen ratio (268.12±28.44 vs 238.28±30.04) and lower partial pressure of arterial blood carbon dioxide (38.02±8.84 vs 49.27±7.84 mmHg) than those in the standard oxygen mask group. The dyspnea score and inflammatory-related parameters in the HFNC group were significantly lower than those in the standard oxygen mask group. The incidence of adverse events was lower in the HFNC group than in the standard oxygen mask group. Conclusion HFNC therapy relieves clinical symptoms more quickly than a standard oxygen mask and reduces the incidence of adverse events.

Cardiopulmonary Exercise Testing to Assess Persistent Symptoms at 6 Months in People With COVID-19 Who Survived Hospitalization – A Pilot Study

Objective The aim of this pilot study was to assess physical fitness and its relationship with functional dyspnea in survivors of Covid-19, 6 months after their discharge from the hospital. Methods Data collected routinely from people referred for cardiopulmonary exercise testing (CPET) following hospitalization for Covid-19 were retrospectively analyzed. Persistent dyspnea was assessed using the modified Medical Research Council dyspnea (mMRC) scale. Results Twenty-three people with persistent symptoms were referred for CPET. Mean mMRC dyspnea score was 1 (SD = 1) and was significantly associated with VO2peak (%) (rho = −0.49). At 6 months, those hospitalized in the general ward had a slightly reduced VO2peak (87% [SD = 20]), whereas those who had been in the intensive care unit (ICU) had a moderately reduced VO2peak (77% [SD = 15]). Of note, the results of the CPET revealed that, in all patients, respiratory equivalents were high, power-to-weight ratios were low, and those who had been in the ICU had a relatively low ventilatory efficiency (mean VE/VCO2 slope = 34 [SD = 5]). Analysis of each individual showed that none had a breathing reserve &lt;15% or 11 L/min, all had a normal exercise electrocardiogram, and 4 had a heart rate above 90%. Conclusion At 6 months, persistent dyspnea was associated with reduced physical fitness. This study offers initial insights into the mid-term physical fitness of people who required hospitalization for Covid-19. It also provides novel pathophysiological clues about the underlaying mechanism of the physical limitations associated with persistent dyspnea. Those with persistent dyspnea should be offered a tailored rehabilitation intervention, which should probably include muscle reconditioning, breathing retraining, and perhaps respiratory muscle training. Impact This study is the first to show that a persistent breathing disorder (in addition to muscle deconditioning) can explain persistent symptoms 6 months after hospitalization for Covid-19 infection and suggests that a specific rehabilitation intervention is warranted.

MILK AGGRAVATES ASTHMA – THE TRUTH OR THE PERCEPTION

Objective: To assess the notion that milk can cause or aggravate asthma and break this myth. Study Design: A cross sectional study. Place and Duration of Study: Medicine department, Combined Military Hospital Lahore, from Jan 2019 to Dec2020. Methodology: A survey was conducted whereby known asthmatics were questioned about their opinion weather milk aggravates their asthma. Those who confirmed their positive response were exposed to milk and some liquid resembling milk, and their Lung functions were tested after each drink. The 42 patients who considered milk as the primary aggravator were called for the study for spirometry Results: A total of 600 people from the general population were surveyed. Two hundred and six (34.3%) of them were illiterate, 394 (65.6%) were educated from middle to graduates. In the first milk/milk encounter, the combined dyspnea scale showed increase of 50.3% and improvement of 0.008% in FEVI/FVC. In the second substitute/milk encounter, the dyspnea score showed an increase of 61.8% and an increase of 0.90% in FEVI/FVC. In the third milk/substitute encounter the dyspnea score showed a decrease of 22.9% and the FEVI/FVC decreases by 5.5%. In the 4th substitute/substitute encounter, dyspnea scores decreased by 8.4% while the pre and postencounter FEVI/ FVC scores were 2726 and 2711 with 0.55% decrease with insignificant p-value >0.05. Conclusion: Drinking milk or milk substitute has negligible effect on the spirometric parameters.

Dyspnea, effort and muscle pain during exercise in lung transplant recipients: an analysis of their association with cardiopulmonary function parameters using machine learning

Background Despite improvement in lung function, most lung transplant (LTx) recipients show an unexpectedly reduced exercise capacity that could be explained by persisting peripheral muscle dysfunction of multifactorial origin. We analyzed the course of symptoms, including dyspnea, muscle effort and muscle pain and its relation with cardiac and pulmonary function parameters during an incremental exercise testing. Methods Twenty-four bilateral LTx recipients were evaluated in an observational cross-sectional study. Recruited patients underwent incremental cardio-pulmonary exercise testing (CPET). Arterial blood gases at rest and peak exercise were measured. Dyspnea, muscle effort and muscle pain were scored according to the Borg modified scale. Potential associations between the severity of symptoms and exercise testing parameters were analyzed using a Forest-Tree Machine Learning approach, which accomplishes for a ratio between number of observations and number of screened variables less than unit. Results Dyspnea score was significantly associated with maximum power output (WR, watts), and minute ventilation (VE, L/min) at peak exercise. In a controlled subgroup analysis, dyspnea score was a limiting symptom only in LTx recipients who reached the higher levels of WR (≥ 101 watts) and VE (≥ 53 L/min). Muscle effort score was significantly associated with breathing reserve as percent of maximal voluntary ventilation (BR%MVV). The lower the BR%MVV at peak exercise (< 32) the higher the muscle effort perception. Muscle pain score was significantly associated with VO2 peak, arterial [HCO3−] at rest, and VE/VCO2 slope. In a subgroup analysis, muscle pain was the limiting symptom in LTx recipients with a lower VO2 peak (< 15 mL/Kg/min) and a higher VE/VCO2 slope (≥ 32). Conclusions The majority of our LTx recipients reported peripheral limitation as the prevalent reason for exercise termination. Muscle pain at peak exercise was strictly associated with basal and exercise-induced metabolic altered pathways. The onset of dyspnea (breathing effort) was associated with the intensity of ventilatory response to meet metabolic demands for increasing WR. Our study suggests that only an accurate assessment of symptoms combined with cardio-pulmonary parameters allows a correct interpretation of exercise limitation and a tailored exercise prescription. The role and mechanisms of muscle pain during exercise in LTx recipients requires further investigations.