Improvement In Dyspnea Research Articles

The Use of High-Flow Nasal Cannula Oxygen Outside the ICU.

High-flow nasal cannula (HFNC) oxygen therapy is a routine, evidence-based treatment in the ICU. Due to its ease of application, non-evidence-based use of HFNC has spread to non-ICU wards. This study reports on the experience with HFNC outside the ICU. This is an observational study of HFNC prescribed by treating physicians in non-ICU areas. Primary outcomes included change in dyspnea visual analog scale score and physiological variables both before and 30 min after initiation of HFNC treatment. Secondary outcomes included mortality, ICU admission, and intubation. We observed decreased median (interquartile range) visual analog scale scores after initiation of HFNC: 8 (6-9) versus 5 (4-6) (P < .001) in 90 of 111 subjects (81%, 95% CI 72.5-87.9%, P < .001). Breathing frequency (31 ± 10 vs 26 ± 7 breaths/min, P < .001) and saturation (84 ± 12% vs 94 ± 5%, P < .001) also improved. Overall cohort mortality was 55 of 111 subjects (50%); however, 41 of 111 subjects (33%) had a do not resuscitate (DNR) order. Among 70 non-DNR subjects, early mortality (< 72 h) occurred in 9 of 70 subjects (13%), and late mortality in 12 of 70 subjects (17%). The composite end point (ie, discharged alive, non-intubated, not admitted to ICU) was met by 35 of 70 subjects (50%) without a DNR order. An increased ROX index ([SpO2 /FIO2 ]/breathing frequency) was the only independent predictor associated with achieving the composite outcome (odds ratio 1.51, 95% CI 1.1-2.0, P = .01). Higher pre-connection visual analog scale score (odds ratio 1.75, 95% CI 1.35-2.28, P < .001) and a history of respiratory disease (odds ratio 3.52, 95% CI 1.27-9.72, P = .01) were predictors of greater improvement in dyspnea with HFNC. No variable predicted mortality. HFNC outside the ICU was associated with improved visual analog scale score, breathing frequency, and saturation but with a relatively high mortality, even in non-DNR subjects. HFNC was used in many subjects who had a DNR order. This therapy may have been palliative in intent. Care should be exercised in using this therapy in a setting that is not continuously monitored.

Effect of complementary Integrative Oncology on anxiety, depression and quality of life in thoracic cancer patients: A pilot study

PurposeThoracic-cancer (TC) patients have an extensive toll taken in terms of health-related quality of life (HRQL). Integrative Oncology (IO) is recognized as a valid complement to any Standard-Therapy treatment to improve outcomes in TC patients. The objective of this pilot-study was to evaluate the effect of adding IO (acupuncture, Cognitive-Behavior Therapy and mindfulness) in terms of depression, anxiety and HRQL. MethodsTC patients who attended the Thoracic Oncology-Unit from July to September 2018 were invited to participate. A total of 16 patients were included in the study, 8 patients were required to attend 5 weekly sessions of IO and 8 patients were invited as controls. Anxiety, depression and HRQL were measured at baseline and after completing 5 sessions of IO or 5 weeks, using the HADS scale and the QLQ-C30 scale. ResultsA total of 8 patients in the IO group attended the 5 sessions and 8 patients were followed as controls. Compliance with the therapies was high, none of the patients dropped out from the study. A tendency for improvement in anxiety, fatigue, pain and dyspnea was observed in patients attending IO, though not statistically significant likely due to sample size. ConclusionsIO therapies are well accepted among TC patients. Larger studies are necessary with robust sample sizes to improve conclusions regarding outcome improvements.

Value of machine learning in predicting TAVI outcomes.

BackgroundTranscatheter aortic valve implantation (TAVI) has become a commonly applied procedure for high-risk aortic valve stenosis patients. However, for some patients, this procedure does not result in the expected benefits. Previous studies indicated that it is difficult to predict the beneficial effects for specific patients. We aim to study the accuracy of various traditional machine learning (ML) algorithms in the prediction of TAVI outcomes.Methods and resultsClinical and laboratory data from 1,478 TAVI patients from a single centre were collected. The outcome measures were improvement of dyspnoea and mortality. Three experiments were performed using (1) screening data, (2) laboratory data, and (3) the combination of both. Five well-established ML techniques were implemented, and the models were evaluated based on the area under the curve (AUC). Random forest classifier achieved the highest AUC (0.70) for predicting mortality. Logistic regression had the highest AUC (0.56) in predicting improvement of dyspnoea.ConclusionsIn our single-centre TAVI population, the tree-based models were slightly more accurate than others in predicting mortality. However, ML models performed poorly in predicting improvement of dyspnoea.Electronic supplementary materialThe online version of this article (10.1007/s12471-019-1285-7) contains supplementary material, which is available to authorized users.

The other explanation for dyspnea: giant paraesophageal hiatal hernia repair routinely improves pulmonary function

Paraesophageal hiatal hernias (PEHs) are most commonly associated with gastrointestinal symptoms; less widely appreciated is their potentially important influence on respiratory function. We hypothesize that surgical repair of PEH will significantly improve not only gastrointestinal symptoms, but also preoperative dyspnea and spirometry scores. A prospective Institutional Review Board-approved database was used to review all patients undergoing PEH repair from 2000 to 2016. Patients with pre- and postoperative pulmonary function tests assessed by spirometry were included. Postoperative changes in spirometry measurements were compared to PEH size as reflected by the percentage of intrathoracic stomach observed on preoperative contrast studies. Patients were stratified according to improvement in forced expiratory volume in 1 second (FEV1). Patients with >12% ('significant') improvement in FEV1 after surgery were compared to the remaining patient population. In total, 299 patients met the inclusion criteria. Symptomatic improvement in respiratory function was noted in all patients after PEH repair. Age, gender, BMI, presenting symptoms, Charlson comorbidity index as well as preoperative comorbidities did not significantly impact the functional outcome. Spirometry results improved in 80% of the patients, 21% of whom showed an improvement of >20% compared to the preoperative level. 'Significant' improvement in respiratory function was seen in 122 of 299 (41%) patients. Patients presenting with moderate and severe preoperative pulmonary obstruction demonstrated 'significant' improvement in FEV1 in 48% and 40% of cases, respectively. Large PEHs, characterized by a percentage of intrathoracic stomach >75%, was strongly associated with 'significant' improvement in FEV1 (P = 0.001). PEHs can impact subjective and objective respiratory status and surgical repair can result in a significant improvement in dyspnea and pulmonary function score that is independent of preoperative pulmonary disease. Gastric herniation of more than 75% was associated with higher possibility for improvement of pulmonary function tests. Patients with persistent and unexplained dyspnea and coexistent PEH should be assessed by an experienced surgeon for consideration of elective repair.

Fan Therapy for the Treatment of Dyspnea in Adults: A Systematic Review

ContextThe use of a handheld or electric fan has been proposed as one component of the complex clinical interventions used in the relief of dyspnea; however, there is a lack of consensus regarding its efficacy. ObjectivesWe performed a systematic review to determine the effectiveness of fan therapy for the treatment of dyspnea. MethodsWe searched the Medline, EMBASE, Web of Science, Scopus, CINAHL, PsycInfo, and Cochrane Library databases to identify all fan therapy studies published from January 1, 1946 to September 31, 2018. The search terms included “dyspnea,” “dysponea,” “dyspneic,” “short of breath,” “shortness of breath,” “breathless,” “breathlessness,” “breathing difficulty,” “labored breathing,” and “fan.” Searches were limited to articles in English or Chinese. The bibliographies of identified articles were also manually searched. Three authors independently assessed papers for inclusion. ResultsTen of the 92 unique records identified met the inclusion criteria (nine randomized controlled trials and one cohort study). Most studies (80%) were conducted in the hospital setting, and none were double blinded. Nearly half (159 [46%]) of the 344 total subjects had cancer. The most common nonmalignant disease was chronic obstructive pulmonary disease. The most common duration of fan therapy was five minutes. Six studies (60%) reported a significant improvement in dyspnea with fan therapy. There are two ongoing trials being conducted based on a search of trial registries. ConclusionLimited direct evidence from randomized controlled trials indicates that fan therapy may effectively alleviate dyspnea. Additional trials are warranted to confirm this finding and explore the use of fan therapy for the treatment of dyspnea in more diverse populations and settings.

Treatment of complex airway stenoses using patient-specific 3D-engineered stents: a proof-of-concept study

Anatomically complex airway stenosis (ACAS) represents a challenging situation in which commercially available stents often result in migration or granulation tissue reaction due to poor congruence. This proof-of-concept clinical trial...

Maximizing quality of life remains an ultimate goal in the era of precision medicine: exemplified by lung cancer.

An ultimate goal of precision medicine in lung cancer treatment is to restore patient health with maximized quality of life (QOL). Results from Mayo Clinic studies show that a significant improvement in fatigue, dyspnea, and pain scales could lead to better overall QOL. Although treatments and guidelines for clinical implementation to alleviate these key symptoms are available, few cancer patients receive adequate therapy, mostly because of limitations in current care delivery systems and unclear clinicians’ roles. For optimal care of lung cancer survivors in different subpopulations, three barriers must be overcome: physicians’ lack of knowledge, unwarranted practice variation, and uncertainty regarding care provider roles. Appropriate culturally adapted, tested and validated tools for QOL measures must be developed, rather than directly translating existing tools between different languages and across cultures or diverse subpopulations. Finally, lack of sensitive, adequate, and relevant tools in measuring health-related QOL (HRQOL) has long been an issue for effective data collection, demanding a global consensus on a set of core components that reflect the needs of all critical parties for the best cure and care, supporting patients to achieve optimal HRQOL.

Application of Micro-Tech stents in malignant carinal stenosis.

Malignant carinal stenosis is a disease process that is not always suitable for treatment with a Y-shaped stent. When one of the main bronchi is completely obstructed and cannot be recanalized, or its distal lung tissue has lost function, inserting a Y-shaped stent is infeasible. In this complex condition, a cone-shaped stent is selected to maintain the patency of the trachea and the other main bronchus. The efficacy of the bare cone-shaped Micro-Tech stent to treat malignant carinal stenosis was evaluated in the current study. The medical records of 47 patients with malignant carinal stenosis who underwent Micro-Tech stent placement between January 2004 and October 2017 in Beijing Tian Tan Hospital (Beijing, China) were analyzed retrospectively. A total of 47 bare Micro-Tech stents (28 Y-shaped and 19 cone-shaped) were successfully inserted in the patients. Following stent placement, immediate satisfactory results were achieved in all patients, especially an improvement of dyspnea (100%), cough (81.1%) and stridor (100%). The Karnofsky scores were significantly increased (P<0.001), and the American Thoracic Society Dyspnea Index values were significantly decreased (P<0.001). Following a median of 88 days, initial bronchoscopic interventions were performed for tumor overgrowth (84.6%), stent fracture (7.7%) and granulation tissue (7.7%). Restenting was performed in two patients due to tumor progression (n=1) and stent fracture (n=1). Removal of a Y-shaped stent was attempted in one patient, but failed, as the stent had become partly embedded in the airway mucosa. In conclusion, cone-shaped Micro-Tech stent placement maintained tracheal-unilateral main bronchus patency and benefitted patients with malignant carinal stenosis in whom Y-shaped stents were not suitable for insertion.

Suture lateralisation plus arytenoid cartilage release for treating bilateral vocal fold immobility with mechanical fixation.

SUMMARYA suture lateralisation (SL) instead of an endolaryngeal tissue ablation procedure under endoscopy has been utilised to treat bilateral vocal fold immobility (BVFI) since 1980. However, mechanical fixation (MF) of the cricoarytenoid joint (CAJ) has continually challenged the effectiveness of glottic dilatation both in the SL procedure and the tissue ablation procedure. From 2007 to 2015, a total of 38 patients with BVFI underwent 40 exo-endolaryngeal suture lateralisation (exoeSL) procedures and three were diagnosed with MF in our hospital. For these MF, we introduced an external approach method to release the CAJ followed by a similar exoeSL procedure. The CAJ release procedure enabled the preservation of the endolaryngeal mucous membrane (ELM) and consequently spared the use of laser surgery. All three CAJ release procedures led to decannulations (one patient) or improvement of dyspnoea (two patients). The difference between the exoeSL and the endo-exolaryngeal suture lateralisation (endoeSL) procedure is discussed based on their effectiveness in MF management.

Abstract B161: Pseudoprogression of metastatic abdominal wall nodules in a patient with lung carcinoma treated with pembrolizumab

Abstract Pembrolizumab is a humanized IgG4 Kappa monoclonal programmed death receptor 1 directed antibody FDA approved for the first line treatment of metastatic non-small cell lung carcinoma (NSCLC) expressing &amp;gt;=50% PD-L1. Pseudoprogression in this context has rarely been reported. We encountered a patient within our community practice who received treatment with pembrolizumab and demonstrated radiologic features of pseudoprogression initially followed by clinical progression where upon histologic evaluation favored pseudoprogression over progression. The aims of this study are as follows: Firstly, to describe the clinico-pathologic-radiologic aspects of this patient’s treatment journey; secondly, to histologically characterize a lesion that was biopsied which showed clinical features of progression, but histologically, pseudoprogression; thirdly, to perform detailed flow cytometric analysis of lymphocytes obtained through the biopsy to characterize pseudoprogression. This is a single patient case study performed by reviewing clinical notes, radiology, and histology. Samples obtained on biopsy were further characterized by flow cytometry. A 72-year-old male patient with small volume metastatic squamous cell lung carcinoma with a tumor proportion score of 100% for PD-L1, was initially treated with radiation (20Gy) to palliate worsening dyspnea caused by airway obstruction. He had good local control with improvement in dyspnea and subsequently requested for observation only. Serial imaging revealed the development of an abdominal wall nodule. Before long, his metastatic disease became symptomatic and he was treated with first line pembrolizumab. Three weeks after his first dose, he presented with severe abdominal wall pain and a new palpable abdominal wall mass. Imaging performed confirmed the presence of a new abdominal wall mass in contrast to a reduction in size of his pulmonary lesions. This was thus assessed as pseudoprogression, and he was continued on treatment with radiologic response noted three weeks later in all lesions. He discontinued treatment due to cost at this point, and subsequently restarted treatment upon radiologic progression of disease. On restarting treatment, his abdominal wall nodule increased in size and ulcerated. True tumor progression was considered prompting biopsy of the abdominal wall nodule to enable stratification into clinical trials. However, histologic evaluation showed chronically inflamed granulation tissue with no microscopic evidence of malignancy suggesting pseudoprogression once again instead. The patient went on to receive radiotherapy to the abdominal wall nodule, and a serial scan demonstrated a reduction in size of the abdominal wall nodule and stable pulmonary disease. Flow cytometric analysis of biopsy tissue revealed predominantly CD45+ cells, 69.5% of which were CD3+. CD45+CD3+CD56- cells comprised CD4+ (27.9%), CD8+ (64.9%), CD4+PD1+ (46.7%), CD8+PD+ (37.7%). Further analysis by flow and mass cytometry is ongoing, and attempts are also being made to assess the tumor antigen specificity of the T-cells. In a patient with clinically immunogenic cancer responding to intermittent anti-PD1 therapy, we observed varying clinico-radiologic responses across his metastatic lesions, and a pathologic evaluation of a clinically progressing lesion revealed pseudoprogression instead. Citation Format: Tiffany Hennedige, Daniel Tan, Narayanan Gopalakrishna Iyer, Amit Jain. Pseudoprogression of metastatic abdominal wall nodules in a patient with lung carcinoma treated with pembrolizumab [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr B161.

Malignant Pleural Effusion: Still a Long Way to Go.

Malignant pleural effusion, which is a common clinical problem in patients with cancer, may be due to both primary thoracic tumours or to a metastatic spread in the chest and constitutes the first sign of disease in approximately 10% of patients. Almost all cancers can potentially produce a pleural effusion. The presence of malignant tumour cells in the pleural fluid is generally indicative of advanced disease and is associated with high morbidity and mortality with reduced therapeutic options. Dyspnoea during mild physical activity or at rest is generally the typical sign of restrictive respiratory failure. This is a systematic review of all the main articles in the English language on the topic of malignant pleural effusion and reported by the Pubmed database from 1959 to 2018. I reviewed the literature and guidelines with the aims to focus on what is known and on future pathways to follow the diagnosis and treatment of malignant pleural effusions. The main goal of palliation of a malignant pleural effusion is a quick improvement in dyspnoea, while thoracentesis under ultrasound guidance is the treatment of choice for patients with a limited life expectancy or who are not candidates for more invasive procedures such as drainage using an indwelling small pleural catheter, chemical pleurodesis with sclerosing agents, pleurectomy or pleuro-peritoneal shunt. Despite progress in therapeutic options, the prognosis remains severe, and the average survival is 4-9 months from the diagnosis of malignant pleural effusion. Moreover, mortality is higher for patients with malignant pleural effusion compared with those with metastatic cancer but no malignant pleural effusion. Therefore, the prognosis of these patients primarily depends on the underlying disease and the extension of a primary tumour. This review focuses on the most relevant updates in the management of malignant pleural effusion.

Patent Foramen Ovale and Hypoxemia.

Patent foramen ovale (PFO), an embryonic remnant of the fetal circulation, is present in 20-25% of adults. Although recent observational studies and clinical trials have established the link between PFO-mediated right-to-left shunting with cryptogenic stroke and migraine with aura, the role of a PFO in exacerbating hypoxemic medical conditions (ie, sleep apnea, chronic obstructive pulmonary disease, pulmonary hypertension, platypnea-orthodeoxia, pulmonary arteriovenous malformation, high-altitude pulmonary edema, and exercise desaturation) remains less understood. PFO-mediated hypoxemia occurs when deoxygenated venous blood from the right atrium enters and mixes with oxygenated arterial blood in the left atrium. Patients with an intracardiac right-to-left shunt may have profound hypoxemia out of proportion to underlying primary lung disease, even in the presence of normal right-sided pressures. The presence of right-to-left cardiac shunting can exacerbate the degree of hypoxemia in patients with underlying pulmonary disorders. In a subset of these patients, percutaneous PFO closure may result in marked improvement in dyspnea and hypoxemia. This review discusses the association between PFO-mediated right-to-left shunting with medical conditions associated with hypoxemia and explores the role of percutaneous PFO closure in alleviating the hypoxemia.

Cryotherapy and electrocautery in the management of malignant endobronchial neoplasms

Background Central airway obstruction is a problem facing all medical and surgical specialists caring for patients with chest diseases. Bronchoscopic cryotherapy (CRYO) and electrocautery (EC) are two different techniques used for the management of endobronchial lesions, and they have a role in palliative treatment of malignant central airway lesions. Aim The aim of the work was to compare between CRYO and EC in the management of malignant endobronchial neoplasms. Patients and methods A prospective study was conducted on 40 patients with malignant endobronchial mass who were selected for bronchoscopic CRYO and EC. Thirty-one men and nine women, with age range from 25 to 65years were included in this study. Bronchoscopic CRYO and EC were performed under local anesthesia using a flexible fiberoptic bronchoscope. Results CRYO and EC procedures provided significant improvement of dyspnea (P Conclusion EC and CRYO are effective modalities of endobronchial debulking in the treatment of central airway obstruction associating endobronchial malignancy. They relieve symptoms, improve pulmonary function tests, arterial blood gas parameters, and quality of life in a significant way; moreover they are easy, safe, and cheap with minimal complications.

Comprehensive Lung Function Assessment Does not Allow to Infer Response to Pulmonary Rehabilitation in Patients with COPD.

The degree of lung function is frequently used as referral criterion for pulmonary rehabilitation. The efficacy of pulmonary rehabilitation was assessed in 518 chronic obstructive pulmonary disease (COPD) patients, after clustering based on a comprehensive pre-rehabilitation lung function assessment. Mean improvements in dyspnea, exercise performance, health status, mood status and problematic activities of daily life after pulmonary rehabilitation were mostly comparable between the seven clusters, despite significant differences in the degree of lung function. The current study demonstrates no significant relationship between the seven lung-function-based clusters and response to pulmonary rehabilitation. Therefore, baseline lung function cannot be used to identify those who will respond well to pulmonary rehabilitation, and moreover, cannot be used as a criterion for referral to pulmonary rehabilitation in patients with COPD.

Intravenous treprostinil via an implantable pump in pediatric pulmonary arterial hypertension

Intravenous prostacyclin-based therapy improves survival in children with pulmonary arterial hypertension (PAH), but is typically administered via an external infusion pump, which places a considerable burden on the patient. Implanted pumps may overcome some of the limitations of external pumps. We describe the first long-term use of an implanted pump for intravenous treprostinil delivery in a pediatric patient with PAH. Our patient was experiencing marked dyspnea on exertion despite triple combination therapy with bosentan, sildenafil, and inhaled iloprost. Parenteral prostacyclin-based therapy was discussed and the patient rejected options involving external pumps; she finally chose intravenous treprostinil delivery via an implanted pump (LENUS Pro®; fixed flow rate; 20 ml reservoir). The patient underwent pump implantation in July 2012 (aged 14 years) under general anesthesia with no peri- or postoperative complications. She showed marked improvements in fatigue and dyspnea over the subsequent weeks, and her inhaled iloprost regimen was slowly decreased and stopped after six months. During follow-up, the pump showed an unexpected, progressive increase in flow rate that allowed a treprostinil dose of 170 ng/kg/min to be achieved, but at the cost of shortened intervals between refills. The pump was therefore replaced in August 2017 with a newer model with an adjustable flow rate (Siromedes®). A catheter dislocation was corrected under local anesthesia one week after the replacement surgery. The patient is currently receiving treprostinil 170 ng/kg/min with percutaneous refills every 12–13 days. Thus, implantable pumps might be a valuable alternative to external pumps for treprostinil infusion in pediatric PAH.

The Efficacy, Safety, and Tolerability of Additional Serelaxin Administration to Standard Therapy in Asian Patients with Acute Heart Failure: The RELAX-AHF-ASIA trial

Background Acute heart failure (AHF) is associated with a high risk of post-discharge rehospitalisation and mortality. Existing evidence suggested potential therapeutic benefits of serelaxin in patients with AHF, although corresponding data in Asian patients remained scarce. RELAX-AHF-ASIA, a multinational, randomised, double-blind, placebo-controlled, Phase III trial, evaluated the effects of serelaxin on symptom relief and clinical outcomes in Asian AHF patients. Methods Patients diagnosed with AHF based on clinical criteria regardless of ejection fraction, with a systolic blood pressure ≥125 mmHg and mild-to-moderate renal dysfunction were randomised within 16 hours of presentation to receive 48-hour intravenous infusion of 30 μg/kg/day serelaxin or placebo in addition to standard therapy. The patients were followed-up for up to 180 days. A novel trichotomous primary endpoint was used in the RELAX-AHF-ASIA trial. It included: (1) treatment success (moderate/marked improvement in patient-reported dyspnoea and physician-assessed signs of congestion on Day 2); (2) treatment failure (in-hospital worsening of signs and/or symptoms of heart failure [HF] requiring intensification of intravenous HF therapy or mechanical ventilation, renal/circulatory support, rehospitalisation due to HF/renal failure or death through Day 5) and (3) unchanged status. Secondary endpoints included time to in-hospital worsening HF through Day 5 and all-cause and cardiovascular deaths through Day 180. Results Although the trial aimed to randomise 1520 AHF patients, it was prematurely terminated following the neutral read-out of the large phase III RELAX-AHF-2 trial. A total of 876 patients were randomised in the RELAX-AHF-ASIA trial and the final analysis was performed with 870 patients (serelaxin, 437; placebo, 433). The trial was conducted at 127 centres in 11 countries: (China, 15; India, 7; Japan, 50; Republic of Korea, 14; Malaysia, 7; Philippines, 9; Singapore, 2; Jordan, 3; Lebanon, 4; Taiwan, 10; Thailand, 6). The mean age was 70 years and 64% of patients were men. The demographics and baseline characteristics were well balanced between treatment groups. Due to premature termination of this trial, only exploratory analysis for primary and secondary endpoints was performed. The proportion of patients with treatment failure was less in the serelaxin group (4.1%) than in the placebo group (8.3%), but the primary endpoint failed to achieve statistical significance. Serelaxin significantly reduced in-hospital worsening HF through Day 5 with a hazard ratio of 0.41 (95% confidence interval: 0.20, 0.84; P=0.0119), using a Cox-regression model. There was no difference in time to cardiovascular mortality and all-cause mortality through Day 180. No new or unexpected safety findings were reported in this trial. The frequency of serious adverse events was similar between groups, and serelaxin infusion was well tolerated. Conclusion The RELAX-AHF-ASIA as the first randomised clinical trial specifically in Asian AHF patients represents a landmark trial in Asia. Although the trial was prematurely terminated, it demonstrated that serelaxin was well tolerated and that it improved a novel trichotomous primary endpoint, albeit not statistically, compared with placebo. Exploratory analysis revealed that worsening HF significantly improved with serelaxin treatment. Although RELAX-AHF-ASIA could not confirm the primary endpoint, it demonstrated that future clinical trials of AHF could be successfully conducted in Asian countries.

Longitudinal Changes in Quantitative Interstitial Lung Disease on Computed Tomography after Immunosuppression in the Scleroderma Lung Study II.

The Scleroderma Lung Study II (SLS II) demonstrated significant improvements in pulmonary function and dyspnea at 24 months compared with baseline when patients with symptomatic scleroderma-related interstitial lung disease (SSc-ILD) were treated with either cyclophosphamide for 1 year (followed for another year on placebo) or mycophenolate mofetil for 2 years in a randomized, double-blind clinical trial. Physiologic and clinical outcomes of SLS II have been published previously. The aim of the study was to assess changes from baseline in the extent of SSc-ILD on high-resolution computed tomography (HRCT) measured in the SLS II participants using quantitative image analysis after 2 years and to determine whether these HRCT changes were correlated with the changes in physiologic and clinical measures over the same time interval. Ninety-seven of the 142 randomized subjects (cyclophosphamide group, 47 subjects; mycophenolate mofetil group, 50 subjects) participating in SLS II underwent thoracic volumetric thin-section HRCT at both baseline and 24 months. Quantitative computer-aided diagnosis scores using volumetric HRCT scans were obtained using a previously developed computer-aided system. The scores were quantitative lung fibrosis, quantitative ground glass, quantitative honeycomb, and quantitative interstitial lung disease (QILD), the latter representing the sum of quantitative lung fibrosis, quantitative ground glass, and quantitative honeycomb. These scores were obtained both for the whole lung and for individual lobes. Paired t tests were used for the combined (pooled) cyclophosphamide and mycophenolate mofetil groups to compare 24-month changes from baseline in both the whole lung and the lobe of maximal involvement as determined at baseline (worst lobe). At the end of the 24-month trial, QILD in the whole lung was significantly reduced by a mean of 2.51% in the pooled groups (adjusted 95% confidence interval, -4.00 to -1.03%; P = 0.001). There was no significant difference in the QILD score improvement between the cyclophosphamide (-2.66%) and mycophenolate (-2.38%) groups when assessed separately (P = 0.88). For the pooled group, the 24-month changes in QILD scores in the whole lung correlated significantly with other outcomes, including 24-month changes in forced vital capacity (ρ = -0.37), single-breath diffusing capacity of the lung for carbon monoxide (ρ = -0.22), and breathlessness as measured by the Transition Dyspnea Index (ρ = -0.26). Treatment of SSc-ILD with either cyclophosphamide for 1 year, followed by placebo for a second year, or mycophenolate for 2 years was associated with a significant reduction (improvement) in the extent of HRCT SSc-ILD assessed by computer-aided diagnosis scores, which correlated well with one or more other measures of treatment response. These findings demonstrate that actual changes in lung structure accompany improvements in physiologic and/or symptomatic measures in SSc-ILD.

Improvement of exertional dyspnea and breathing pattern of inspiration to expiration after bronchial thermoplasty

BackgroundBronchial thermoplasty (BT) is a bronchoscopic treatment that can ameliorate the symptoms of severe asthma. However, little is known about the mechanism by which BT improves exertional dyspnea without significantly changing the resting pulmonary function in asthmatics. To understand the mechanism, cardiopulmonary variables were investigated using cardiopulmonary exercise testing (CPET) in a patient with severe asthma before and after BT.Case presentationA 57-year-old Japanese man visited our hospital for consultation of the intractable asthma, which we managed with three treatment sessions of BT. Comparison of the findings pre-BT and at 1 year after BT demonstrated that (1) the resting tests for respiration showed no improvement in forced expiratory volume in 1 s, but the forced oscillation technique showed decreases in both inhalation and exhalation respiratory resistance values, and (2) the CPET results showed (i) improvement in exertional dyspnea, exercise endurance, and arterial oxygen saturation at the end of exercise; (ii) that the expiratory tidal volume exceeded the inspiratory tidal volume during exercise, which implied that a sufficient exhalation enabled longer inspiratory time and adequate oxygen absorption; and (iii) that an increase in respiratory frequency could be prevented throughout exercise.ConclusionsThis case report described a novel mechanism of BT in improving exertional dyspnea and exercise duration, which was brought about by ventilatory improvements related to the breathing pattern of inspiration to expiration.

Acupuncture for Cancer Pain and Symptom Management in a Palliative Medicine Clinic.

Studies suggest acupuncture improves cancer-related symptoms; however, it is unclear whether patient characteristics predict pain response. This study determined acupuncture's effect on cancer-related pain and identified variables associated with pain response. A retrospective chart review included adult patients with cancer referred to palliative medicine and received acupuncture for pain management. Paired t tests compared differences in pain scores from pre- to postacupuncture. Clinically meaningful pain improvement was defined as ≥2-point reduction in pain score. Logistic regression was used to evaluate associations between patient characteristics and pain improvement. One hundred seventy acupuncture treatments from 68 individual patients were studied. Significant reductions in mean pain scores were observed after the first treatment (-1.9 ± 1.8; P < .001) and across all treatments (-1.7 ± 1.9; P < .001). Multivariable analysis demonstrated clinically meaningful pain improvement with higher baseline pain scores (odds ratio [OR]: 1.79, 95% confidence interval [CI]: 1.44-2.22; P < .001) and stage III/IV disease (OR: 3.23, 95% CI: 1.11-9.40; P < .001). There were significant improvements in anxiety, depression, drowsiness, dyspnea, fatigue, nausea, and well-being after the first treatment and across all treatments ( P < .001). Acupuncture improved cancer-related pain and other symptoms. Those with higher baseline pain scores and advanced disease were more likely to achieve significant pain reduction. Improved depression and fatigue were closely related to pain reduction. Further studies are needed to confirm pain response variables, establish durability, and develop a personalized approach to acupuncture.

Nonspecific interstitial pneumonia: A rare adverse reaction of atorvastatin

Introduction: Statins have been shown to effectively prevent both cardiovascular morbidity and mortality by inhibiting the hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase enzyme. Pulmonary complications are very rare, and can include pneumonitis, pleural effusion, and nonspecific interstitial pneumonia (NSIP). There have been very few previously documented cases of statin-induced fibrotic NSIP.Case report: We present a female with a history of hyperlipidemia on atorvastatin who presented with shortness of breath. Computed tomography scan of the chest revealed interstitial infiltrates with bilateral ground-glass opacities. She underwent a surgical lung biopsy which showed uniform fibrous alveolar septal thickening, scattered collections of alveolar macrophages and inflammation, along with areas of fibrosis. The findings were most suggestive of fibrotic NSIP. Atorvastatin was stopped and she was started on mycophenolic acid with improvement of her symptoms.Discussion: Although rare, the clinician should be aware of possible pulmonary complications of statin therapy. The exact mechanism of injury is unclear, however immunological or toxicological mechanisms are implicated. One case series of statin induced interstitial lung disease showed some improvement of dyspnea with systemic glucocorticoids and termination of statin therapy. Statins, specifically pravastatin, lovastatin, and simvastatin have been associated with drug induced pneumonitis and interstitial lung disease.