Causes of hypercapnic respiratory failure and associated in-hospital mortality.

BACKGROUND AND OBJECTIVE: Hypercapnic respiratory failure (HRF) can occur due to severe respiratory disease but also because of multiple coexistent causes. There are few data on the prevalence of antecedent causes for HRF and the effect of these causes on prognosis, especially where study inclusion has not been biased with respect to primary diagnosis, interventions received or clinical outcome. We sought to determine the prevalence of pre-specified conditions among patients with HRF and to determine the effect of these causes on in-hospital mortality. METHODS: Cross-sectional study of patients with HRF from 2013 to 2017. Inclusion criteria were PaCO2  >45 mm Hg and pH ≤7.45. Causes of interest were identified using diagnosis codes from hospital records. We used directed acyclic graphs to inform logistic regression models for the outcome of in-hospital death. RESULTS: We identified 873 persons with HRF in the study period. Mean (SD) age was 69 years and 50.4% were males. Acidosis (pH <7.35) was present in 488 (55%) cases. Most (83%) had one or more of the following: obstructive lung disease, lower respiratory tract infection, congestive cardiac failure, sleep disordered breathing, neuromuscular disease, opioid or benzodiazepine use. In-hospital mortality was 12.8%. Obstructive lung disease and cardiac failure were associated with a lower risk of death, whereas respiratory tract infection and neuromuscular disease were associated with increased risk of death. CONCLUSION: HRF is associated with a range of potentially causative conditions, which significantly impact hospital survival. Systematic evaluation of patients with HRF may increase detection of treatable comorbidities.

Lung function and atherosclerosis: a cross-sectional study of multimorbidity in rural Uganda.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a leading cause of global mortality. In high-income settings, the presence of cardiovascular disease among people with COPD increases mortality and complicates longitudinal disease management. An estimated 26 million people are living with COPD in sub-Saharan Africa, where risk factors for co-occurring pulmonary and cardiovascular disease may differ from high-income settings but remain uncharacterized. As non-communicable diseases have become the leading cause of death in sub-Saharan Africa, defining multimorbidity in this setting is critical to inform the required scale-up of existing healthcare infrastructure. METHODS: We measured lung function and carotid intima media thickness (cIMT) among participants in the UGANDAC Study. Study participants were over 40 years old and equally divided into people living with HIV (PLWH) and an age- and sex-similar, HIV-uninfected control population. We fit multivariable linear regression models to characterize the relationship between lung function (forced expiratory volume in one second, FEV1) and pre-clinical atherosclerosis (cIMT), and evaluated for effect modification by age, sex, smoking history, HIV, and socioeconomic status. RESULTS: Of 265 participants, median age was 52 years, 125 (47%) were women, and 140 (53%) were PLWH. Most participants who met criteria for COPD were PLWH (13/17, 76%). Median cIMT was 0.67 mm (IQR: 0.60 to 0.74), which did not differ by HIV serostatus. In models adjusted for age, sex, socioeconomic status, smoking, and HIV, lower FEV1 was associated with increased cIMT (ß = 0.006 per 200 mL FEV1 decrease; 95% CI 0.002 to 0.011, p = 0.01). There was no evidence that age, sex, HIV serostatus, smoking, or socioeconomic status modified the relationship between FEV1 and cIMT. CONCLUSIONS: Impaired lung function was associated with increased cIMT, a measure of pre-clinical atherosclerosis, among adults with and without HIV in rural Uganda. Future work should explore how co-occurring lung and cardiovascular disease might share risk factors and contribute to health outcomes in sub-Saharan Africa.

The evolution of pulmonary function in childhood onset Mucopolysaccharidosis type I.

Respiratory outcomes in Mucopolysaccharidosis Type I (MPS I), have mainly focused on upper airway obstruction, with the evolution of the restrictive lung disease being poorly documented. We report the long-term pulmonary function outcomes and examine the potential factors affecting these in 2 cohorts of MPS I patients, those who have undergone Haematopoietic Stem Cell Transplantation (HSCT) and those treated with Enzyme Replacement Therapy (ERT). The results were stratified using the American Thoracic Society (ATS) guidelines. 66 patients, capable of adequately performing testing, were identified by a retrospective case note review, 46 transplanted (45 Hurler, 1 Non-Hurler) and 20 having ERT (17 Non-Hurler and 3 Hurler diagnosed too late for HSCT). 5 patients died; 4 in the ERT group including the 3 Hurler patients. Overall 14% of patients required respiratory support (non-invasive ventilation (NIV) or supplemental oxygen)) at the end of follow up. Median length of follow-up was 12.2 (range = 4.9-32) years post HSCT and 14.34 (range = 3.89-20.4) years on ERT. All patients had restrictive lung disease. Cobb angle and male sex were significantly associated with more severe outcomes in the HSCT cohort, with 49% having severe to very severe disease. In the 17 Non-Hurler ERT treated patients there was no variable predictive of severity of disease with 59% having severe to very severe disease. During the course of follow up 67% of the HSCT cohort had no change or improved pulmonary function as did 52% of the ERT patients. However, direct comparison between therapeutic modalities was not possible. This initial evidence would suggest that a degree of restrictive lung disease is present in all treated paediatrically diagnosed MPS I and is still a significant cause of morbidity, though further stratification incorporating diffusing capacity for carbon monoxide (DLCO) is needed.

Expression of ACE2 in airways: Implication for COVID-19 risk and disease management in patients with chronic inflammatory respiratory diseases.

Coronavirus disease 2019 (COVID-19), caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been a rising international cause of morbidity and mortality. Angiotensin-converting enzyme 2 (ACE2) is identified as a key cell entry receptor for SARS-CoV-2 and suggested to be a limiting factor for viral entry at the initial infection stage. Recent studies have demonstrated that ACE2 expression is highly enriched in nasal epithelial cells and type II alveolar epithelial cells, highlighting the importance of respiratory tract as the primary target site of SARS-CoV-2. The expression of ACE2 in airway epithelial cells is tightly regulated by inflammatory milieu and environmental and internal stimuli. Very recently, ACE2 has been reported to have different expression levels in airways under distinct chronic inflammatory airway diseases, such as chronic obstructive pulmonary disease (COPD) and allergic asthma, which may associate with the COVID-19 risk and affect the management of primary airway diseases. In this review, we focus on the cutting-edge progress in distribution, expression, and regulation of ACE2 in respiratory system in physiological and pathological conditions, and their implication for the development of COVID-19. We also discuss the management of airway diseases, including asthma, COPD, allergic rhinitis, and rhinosinusitis in the era of COVID-19.

Club Cell Secretory Protein Deficiency Leads to Altered Lung Function.

RATIONALE: CC16 (club cell secretory protein-16), a member of the secretoglobin family, is one of the most abundant proteins in normal airway secretions and has been described as a serum biomarker for obstructive lung diseases. OBJECTIVES: To determine whether low CC16 is a marker for airway pathology or is implicated in the pathophysiology of progressive airway damage in these conditions. METHODS: Using human data from the birth cohort of the Tucson Children's Respiratory Study, we examined the relation of circulating CC16 levels with pulmonary function and responses to bronchial methacholine challenge from childhood up to age 32 years. In wild-type and CC16-/- mice, we set out to comprehensively examine pulmonary physiology, inflammation, and remodeling in the naive airway. MEASUREMENTS AND MAIN RESULTS: We observed that Tucson Children's Respiratory Study participants in the lowest tertile of serum CC16 had significant deficits in their lung function and enhanced airway hyperresponsiveness to methacholine challenge from 11 years throughout young adult life. Similarly, CC16-/- mice had significant deficits in lung function and enhanced airway hyperresponsiveness to methacholine as compared with wild-type mice, which were independent of inflammation and mucin production. As compared with wild-type mice, CC16-/- mice had significantly elevated gene expression of procollagen type I, procollagen type III, and α-smooth muscle actin, areas of pronounced collagen deposition and significantly enhanced smooth muscle thickness. CONCLUSIONS: Our findings support clinical observations by providing evidence that lack of CC16 in the lung results in dramatically altered pulmonary function and structural alterations consistent with enhanced remodeling.

External Validation and Recalculation of the CODEX Index in COPD Patients. A 3CIAplus Cohort Study.

The CODEX index was developed and validated in patients hospitalized for COPD exacerbation to predict the risk of death and readmission within one year after discharge. Our study aimed to validate the CODEX index in a large external population of COPD patients with variable durations of follow-up. Additionally, we aimed to recalculate the thresholds of the CODEX index using the cutoffs of variables previously suggested in the 3CIA study (mCODEX). Individual data on 2,755 patients included in the COPD Cohorts Collaborative International Assessment Plus (3CIA+) were explored. A further two cohorts (ESMI AND EGARPOC-2) were added. To validate the CODEX index, the relationship between mortality and the CODEX index was assessed using cumulative/dynamic ROC curves at different follow-up periods, ranging from 3 months up to 10 years. Calibration was performed using univariate and multivariate Cox proportional hazard models and Hosmer-Lemeshow test. A total of 3,321 (87.8% males) patients were included with a mean ± SD age of 66.9 ± 10.5 years, and a median follow-up of 1,064 days (IQR 25-75% 426-1643), totaling 11,190 person-years. The CODEX index was statistically associated with mortality in the short- (≤3 months), medium- (≤1 year) and long-term (10 years), with an area under the curve of 0.72, 0.70 and 0.76, respectively. The mCODEX index performed better in the medium-term (<1 year) than the original CODEX, and similarly in the long-term. In conclusion, CODEX and mCODEX index are good predictors of mortality in patients with COPD, regardless of disease severity or duration of follow-up.

Influenza vaccine for chronic obstructive pulmonary disease (COPD).

BACKGROUND: Influenza vaccinations are currently recommended in the care of people with COPD, but these recommendations are based largely on evidence from observational studies, with very few randomised controlled trials (RCTs) reported. Influenza infection causes excess morbidity and mortality in people with COPD, but there is also the potential for influenza vaccination to cause adverse effects, or not to be cost effective. OBJECTIVES: To determine whether influenza vaccination in people with COPD reduces respiratory illness, reduces mortality, is associated with excess adverse events, and is cost effective. SEARCH METHODS: We searched the Cochrane Airways Trials Register, two clinical trials registries, and reference lists of articles. A number of drug companies we contacted also provided references. The latest search was carried out in December 2017. SELECTION CRITERIA: RCTs that compared live or inactivated virus vaccines with placebo, either alone or with another vaccine, in people with COPD. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data. All entries were double-checked. We contacted study authors and drug companies for missing information. We used standard methods expected by Cochrane. MAIN RESULTS: We included 11 RCTs with 6750 participants, but only six of these included people with COPD (2469 participants). The others were conducted on elderly and high-risk individuals, some of whom had chronic lung disease. Interventions compared with placebo were inactivated virus injections and live attenuated intranasal virus vaccines. Some studies compared intra-muscular inactivated vaccine and intranasal live attenuated vaccine with intra-muscular inactivated vaccine and intranasal placebo. Studies were conducted in the UK, USA and Thailand.Inactivated vaccine reduced the total number of exacerbations per vaccinated participant compared with those who received placebo (mean difference (MD) -0.37, 95% confidence interval (CI) -0.64 to -0.11; P = 0.006; two RCTs, 180 participants; low quality evidence). This was due to the reduction in 'late' exacerbations, occurring after three or four weeks (MD -0.39, 95% CI -0.61 to -0.18; P = 0.0004; two RCTs, 180 participants; low quality evidence). Both in people with COPD, and in older people (only a minority of whom had COPD), there were significantly more local adverse reactions in people who had received the vaccine, but the effects were generally mild and transient.There was no evidence of an effect of intranasal live attenuated virus when this was added to inactivated intramuscular vaccination.Two studies evaluating mortality for influenza vaccine versus placebo were too small to have detected any effect on mortality. However, a large study (N=2215) noted that there was no difference in mortality when adding live attenuated virus to inactivated virus vaccination, AUTHORS' CONCLUSIONS: It appeared, from the limited number of RCTs we were able to include, all of which were more than a decade old, that inactivated vaccine reduced exacerbations in people with COPD. The size of effect was similar to that seen in large observational studies, and was due to a reduction in exacerbations occurring three or more weeks after vaccination, and due to influenza. There was a mild increase in transient local adverse effects with vaccination, but no evidence of an increase in early exacerbations. Addition of live attenuated virus to the inactivated vaccine was not shown to confer additional benefit.

The risk of mycobacterial infections associated with inhaled corticosteroid use.

Inhaled corticosteroid (ICS) use is associated with an increased risk of pneumonia. This study was performed to determine if ICS use is associated with an increased risk of nontuberculous mycobacterial pulmonary disease (NTM-PD) or tuberculosis (TB).We conducted a population-based nested case-control study using linked laboratory and health administrative databases in Ontario, Canada, including adults aged ≥66 years with treated obstructive lung disease (i.e. asthma, chronic obstructive pulmonary disease (COPD) or asthma-COPD overlap syndrome) between 2001 and 2013. We estimated odds ratios comparing ICS use with nonuse among NTM-PD and TB cases and controls using conditional logistic regression.Among 417 494 older adults with treated obstructive lung disease, we identified 2966 cases of NTM-PD and 327 cases of TB. Current ICS use was associated with NTM-PD compared with nonuse (adjusted OR (aOR) 1.86, 95% CI 1.60-2.15) and was statistically significant for fluticasone (aOR 2.09, 95% CI 1.80-2.43), but not for budesonide (aOR 1.19, 95% CI 0.97-1.45). There was a strong dose-response relationship between incident NTM-PD and cumulative ICS dose over 1 year. There was no significant association between current ICS use and TB (aOR 1.43, 95% CI 0.95-2.16).This study suggests that ICS use is associated with an increased risk of NTM-PD, but not TB.

Influence of hypertension, diabetes, hyperlipidemia, and obstructive lung disease on multiple sclerosis disease course.

BACKGROUND: Comorbidities are known to affect multiple sclerosis (MS) patients in a number of ways, including delaying time to diagnosis and reducing health-related quality of life. OBJECTIVE: To determine the impact of hypertension, hyperlipidemia, diabetes mellitus, and obstructive lung disease on disease course in MS patients. METHODS: The Knowledge Program is a database linked to our electronic medical record allowing capture of patient and clinician reported outcomes. Through Knowledge Program query and chart review, we identified all relapsing-remitting MS patients seen between 1 January 2010 and 29 May 2012 and acquired their magnetic resonance imaging (MRI) results and comorbidities. Linear and logistic regression models with adjustment for important covariates were used to determine whether the comorbidities affected outcomes over a 3-year period. RESULTS: Hypertension, diabetes, and obstructive lung disease, but not hyperlipidemia, impacted clinical outcomes, including walking speed, self-reported disability, and depression. Hypertension had the greatest effect. The presence of multiple comorbidities had a cumulative effect on clinical outcomes. MRI outcomes were unaffected by comorbidities. CONCLUSION: This 3-year longitudinal study revealed that all comorbidities tested except hyperlipidemia impacted clinical outcomes and a cumulative effect with multiple comorbidities was observed. Consideration of comorbid conditions is essential in MS patient care.

Postobstructive Pneumonia: An Underdescribed Syndrome.

BACKGROUND: Postobstructive community-acquired pneumonia (PO-CAP) is relatively common in clinical practice. The clinical syndrome is poorly defined, and the role of infection as a cause of the infiltrate is uncertain. We prospectively studied patients with PO-CAP and compared them to a cohort of patients with bacterial community-acquired pneumonia (B-CAP). METHODS: We prospectively studied patients hospitalized for CAP; 5.4% had PO-CAP, defined as a pulmonary infiltrate occurring distal to an obstructed bronchus. Sputum and blood cultures, viral polymerase chain reaction, urinary antigen tests, and serum procalcitonin (PCT) were done in nearly all cases. Clinical and laboratory characteristics of patients with PO-CAP were compared to those of patients with B-CAP. RESULTS: In a 2-year period, we identified 30 patients with PO-CAP. Compared to patients with B-CAP, patients with PO-CAP had longer duration of symptoms (median, 14 vs 5 days;P< .001). Weight loss and cavitary lesions were more common (P< .01 for both comparisons) and leukocytosis was less common (P< .01) in patients with PO-CAP. A bacterial pathogen was implicated in only 3 (10%) PO-CAP cases. PCT was <0.25 ng/mL in 19 (63.3%) patients. Although no differences were observed in disease severity or rates of intensive care unit admissions, 30-day mortality was significantly higher in PO-CAP vs B-CAP (40.0% vs 11.7%;P< .01). CONCLUSIONS: Although there is substantial overlap, PO-CAP is a clinical entity distinct from B-CAP; a bacterial cause was identified in only 10% of patients. Our study has important implications for the clinical recognition of patients with PO-CAP, the role of microorganisms as etiologic agents, and the use of antibiotic therapy.

Clinical and haematological risk factors for cerebral macrovasculopathy in a sickle cell disease newborn cohort: a prospective study.

Children with sickle cell disease (SCD) have a significant vascular morbidity, especially cerebral macrovasculopathy (CV), detectable by transcranial Doppler. This study aimed to identify risk factors for CV using longitudinal biological and clinical data in a SCD newborn cohort followed at the Robert Debre Reference centre (n = 375 SS/Sß(0) ). Median follow-up was 6·8 years (2677 patient-years). Among the 59 children presenting with CV, seven had a stroke. Overall, the incidence of CV was 2·20/100 patient-years [95% confidence interval (95% CI): 1·64-2·76] and the incidence of stroke was 0·26/100 patient-years (95% CI: 0·07-0·46). The cumulative risk of CV by age 14 years was 26·0% (95% CI: 20·0-33·3%). Risk factors for CV were assessed by a Cox model encompassing linear multivariate modelling of longitudinal quantitative variables. Years per upper-airway obstruction [Hazard ratio (HR) = 1·47; 95% CI: 1·05-2·06] or bronchial obstruction (HR = 1·76; 95% CI: 1·49-2·08) and reticulocyte count (HR = 1·82 per 50 × 10(9) /l increase; 95% CI: 1·10-3·01) were independent risk factors whereas fetal haemoglobin level (HR = 0·68 per 5% increase; 95% CI: 0·48-0·96) was protective. Alpha-thalassaemia was not protective in multivariate analysis (ancillary analysis n = 209). Specific treatment for upper or lower-airway obstruction and indirect targeting of fetal haemoglobin and reticulocyte count by hydroxycarbamide could potentially reduce the risk of CV.

Tidal changes in respiratory resistance are sensitive indicators of airway obstruction in children.

RATIONALE: Individual assessment of airway obstruction in preschool-age children requires sensitive and specific lung function methods with low demand of cooperation. Although the forced oscillation technique (FOT) is feasible in young children, conventional measurements of respiratory impedance (Zrs) have limited diagnostic power in individuals. OBJECTIVE: To find descriptors of within-breath Zrs that are sensitive indicators of airway obstruction during tidal breathing in children. METHODS: Zrs was measured with (i) a standard multifrequency FOT (4-26 Hz) to assess the mean values of resistance and reactance for whole breaths and (ii) a 10 Hz signal to track the within-breath changes. Various Zrs measures obtained in healthy children (n=75) and those with acute wheeze (n=31) were investigated with receiver operator characteristic (ROC) analysis. The cut-off values obtained for airway obstruction were then tested in children with recurrent wheeze (n=20) before and after administration of salbutamol. RESULTS: The largest area under the ROC curve (0.95) was observed for the tidal changes of resistance between the zero-flow values (ΔR). The ΔR cut-off value of 1.42 hPa s/L detected airway obstruction with sensitivity of 92% and specificity of 89% in children with acute wheeze and distinguished children with recurrent wheeze (16/20 above the cut-off value) from healthy children (22/23 below the cut-off value). Furthermore, ΔR significantly decreased after salbutamol in wheezy children but remained unchanged in healthy children. CONCLUSIONS: New lung function measure ΔR is able to detect airway obstruction with high sensitivity and specificity and is suitable for use in lung function testing in young children.

The Microenvironment of Lung Cancer and Therapeutic Implications.

The tumor microenvironment (TME) represents a milieu that enables tumor cells to acquire the hallmarks of cancer. The TME is heterogeneous in composition and consists of cellular components, growth factors, proteases, and extracellular matrix. Concerted interactions between genetically altered tumor cells and genetically stable intratumoral stromal cells result in an "activated/reprogramed" stroma that promotes carcinogenesis by contributing to inflammation, immune suppression, therapeutic resistance, and generating premetastatic niches that support the initiation and establishment of distant metastasis. The lungs present a unique milieu in which tumors progress in collusion with the TME, as evidenced by regions of aberrant angiogenesis, acidosis and hypoxia. Inflammation plays an important role in the pathogenesis of lung cancer, and pulmonary disorders in lung cancer patients such as chronic obstructive pulmonary disease (COPD) and emphysema, constitute comorbid conditions and are independent risk factors for lung cancer. The TME also contributes to immune suppression, induces epithelial-to-mesenchymal transition (EMT) and diminishes efficacy of chemotherapies. Thus, the TME has begun to emerge as the "Achilles heel" of the disease, and constitutes an attractive target for anti-cancer therapy. Drugs targeting the components of the TME are making their way into clinical trials. Here, we will focus on recent advances and emerging concepts regarding the intriguing role of the TME in lung cancer progression, and discuss future directions in the context of novel diagnostic and therapeutic opportunities.

A 45-year-old man with shortness of breath and eosinophilia.

A 45-year-old man who presented with dyspnea and chest tightness was found to have obstructive lung disease and eosinophilia of 10,300 eosinophils/µL. The differential diagnosis encompassed causes of primary eosinophilia and secondary eosinophilia associated with pulmonary disease, including asthma, environmental allergic reaction, eosinophilic granulomatosis with polyangiitis, allergic bronchopulmonary aspergillosis, acute eosinophilic pneumonia, chronic eosinophilic pneumonia, parasitic infections, tuberculosis, fungal infection, sarcoidosis, mastocytosis, drug reaction with eosinophilia and systemic symptoms, lymphoproliferative hypereosinophilic syndrome, and myeloproliferative hypereosinophilic syndrome. Infectious workup, fiberoptic bronchoscopy with biopsy, and tests for myeloproliferative mutations help differentiate among these causes. Identifying the underlying cause of eosinophilia is imperative in guiding treatment.

ENDOTHELIAL DYSFUNCTION IN PATIENTS WITH CHRONIC OBSRTRUCTIVE PULMONARY DISEASE WITH CONCOMITANT HYPERTENSION.

In recent years, special attention is paid to comorbid conditions in the clinic of internal diseases. There actively explored the role of endothelial dysfunction as a single unit in the pathological formation of chronic obstructive pulmonary disease (COPD) associated with hypertension. The study involved 145 patients who were carried out the final level of metabolites of nitric oxide (NO2, NO3), S-nitrosothiols, endothelial and inducible NO-synthase. All patients were divided into 3 groups: the first group included 55 patients (35 men and 20 women) who had been diagnosed with COPD with concomitant hypertension - the core group. The average age for this group was 57,6 years (46±68). The comparison group consisted of 45 patients (34 men and 11 women) with isolated course of COPD. The average age for second group was 53,3 years (40±67). The control group consisted of 45 healthy volunteers - 25 men and 20 women. Results of the study of the endothelial dysfunction revealed dynamic change in serum nitrate, nitrite, S-nitrosothiols and activity of eNOS and iNOS as the group of patients with COPD with associated hyperttension and the group of patients with isolated COPD. Informative and prognostic indicators relatively severity of diseases in patients with significant comorbidity may be considered high levels of iNOS and S-nitrosothiols, which indicates the voltage of the functional activity of endogenous antioxidant defense mechanisms in this cohort of persons. The findings suggest that the progression of endothelial dysfunction in comorbidity, which may lead to the current aggravation of diseases and vascular disorders in these patients.

Repeating pulmonary rehabilitation: prevalence, predictors and outcomes.

BACKGROUND AND OBJECTIVE: Pulmonary rehabilitation (PR) is a cornerstone of care in chronic respiratory diseases; yet its benefits diminish over time. Repeating PR may be beneficial; however, little is known about the characteristics and outcomes of repeaters. This study aimed to establish the proportion of repeaters, identify characteristics that predict repetition and compare the magnitude of benefits achieved between initial and subsequent programmes. METHODS: Patients with stable chronic respiratory diseases who attended PR over a 9-year period were included. Outcome measures included the 6-min walk distance (6MWD) and the Chronic Respiratory Disease Questionnaire-Self-Reported (CRDQ-SR). Independent predictors of repeating were identified. RESULTS: Of 296 patients, 59 (20%) repeated PR, most within 1-3 years. Following the initial programme, repeaters had significant decline in 6MWD (-96.1 ± 84.6 m; P < 0.001) and CRDQ-SR scores (mean decline -3.6 points, range -0.1 to -7.9 points; P < 0.005). The improvement in 6MWD was less in the repeat programme compared with the first (38.4 ± 50.7 m vs 67 ± 40.4 m; P = 0.005), while the change in CRDQ-SR was similar in all domains. A chronic obstructive pulmonary disease diagnosis increased the odds of repeating PR (odds ratio (OR) 4.8; P = 0.005) while improved mastery in the initial programme reduced the odds (OR 0.9; P = 0.033). CONCLUSIONS: One in five patients repeated PR, achieving clinically significant improvements in exercise tolerance and quality of life. Patients with small improvements in disease mastery after initial PR were more likely to repeat the programme and may benefit from earlier intervention or longer duration PR.

Time course of inflammation resolution in patients with frequent exacerbations of chronic obstructive pulmonary disease.

BACKGROUND: When exacerbation of chronic obstructive pulmonary disease (AECOPD) occurs frequently, patients have high levels of airway and systemic inflammation and a poor quality of life. This study compared the nature and course of systemic and airway inflammation during AECOPD between patients who experienced frequent exacerbations and those with non-frequent exacerbations. MATERIAL AND METHODS: Consecutive hospitalized patients with AECOPD were recruited and divided into 2 groups according to the frequency of AECOPD they had experienced in the previous year. Frequent exacerbators (defined as 2 or more AECOPD in the previous year) and non-frequent exacerbators (defined as zero or 1 AECOPD in the previous year). Inflammatory (interleukin 6, interleukin 8, myeloperoxidase, and C-reactive protein) and clinical (dyspnea, COPD assessment test (CAT), and peak expiratory flow) indices were assessed on the day of admission before starting therapy, day 7 of treatment, the day of planned discharge (day 10-14), and 8 weeks after discharge. RESULTS: We analyzed data from 135 patients; 78 (57.8%) were non-frequent exacerbators and 57 (42.2%) were frequent exacerbators. In both groups, the inflammatory and clinical indices at day 7, the day of planned discharge (day 10-14), and 8 weeks were significantly improved compared to those at admission. Frequent exacerbators had a smaller reduction in their inflammatory indices and CAT scores between exacerbation onset and all the other time points compared with infrequent exacerbators. CONCLUSIONS: Frequent exacerbators have a reduced response to treatment of AECOPD in terms of inflammatory indices and quality of life.

[Total intravenous anesthesia for a patient with Fukuyama congenital muscular dystrophy undergoing scoliosis surgery].

We described the anesthetic management of a 17-year-old male patient with Fukuyama congenital muscle dystrophy (FCMD) who underwent surgical repair for scoliosis under total intravenous anesthesia. The patient had severe constructive lung disease (%VC 18.6%). Left ventricular wall motion was reduced (left ventricular ejection fraction 40%). Propofol and remifentanil were continuously infused to maintain anesthesia, but we did not use any muscle relaxant throughout the course. We used arterial pressure-based cardiac output and stroke volume variation as a guide for circulatory management. We could not find any congestion on chest X-ray after the surgery. The emergence and recovery from the anesthesia was rapid and muscle strength was enough, and we could extubate the patient just after the end of the surgery. No respiratory and cardiac complications occurred during the postoperative period. Even though he was in the young age in FCMD, respiratory and cardiac complications were severely impaired. For successful anesthetic management in FCMD patient, we should take care of rapid emergence from anesthesia and also we should not impair muscle strength for good postoperative respiratory function. Appropriate hemodynamic monitoring to avoid postoperative cardiac congestion is also required.

[Spinal anesthesia using a low dose of isobaric bupivacaine in a patient with pulmonary artery hypertension and mixed obstructive and restrictive lung disease undergoing repeated femoral fracture surgery].

A 75-year-old woman with primary pulmonary hypertension was on medical therapy and ambulatory oxygen inhalation therapy for 7 years. The patient had right femoral fracture and was admitted to our hospital. She had also suffered from asthma for 2 years, and her vital capacity was 1.35 l with forced expiratory volume in 1 second 0.79 l, and with her mean pulmonary artery pressure 60 mmHg. Open reduction and internal fixation were performed under spinal anesthesia using isobaric bupivacaine 6 mg with fentanyl 10 microg, and the patient was discharged on postoperative 31 day with no major complications. One year after the surgery, she had left femoral fracture, and surgery was performed under spinal anesthesia using isobaric bupivacaine 6 mg with fentanyl 10 microg. With its minimal effects on hemodynamics, we speculate that spinal anesthesia using a low dose of isobaric bupivacaine can be a choice for patients with pulmonary hypertension.

[Assessment and management of chronic cough in adults]. / Toux chronique de l'adulte: evaluation et prise en charge.

Chronic cough is one of the most common symptoms for which outpatient care is sought. The most frequent causes are upper airway cough syndrome, asthma, and gastroesophageal reflux. It is often difficult to determine the origin of chronic cough based on the medical history and physical examination. Empirical treatment directed at the three aforementioned etiologies is thus of considerable value in the initial workup. Treatment failure is most commonly due to insufficient treatment (dosage or duration) or to the coexistence of several causes needing simultaneous use of different drugs.