Remission of hypersensitivity pneumonitis after allogeneic hematopoietic stem cell transplantation.

A 50-year-old man was diagnosed with hypersensitivity pneumonitis caused by the environment of his bar owing to worsening symptoms, laboratory test results, and computed tomography images after an environmental inhalation challenge test. His hypersensitivity pneumonitis exacerbated despite receiving prednisolone 20 mg/day. The patient underwent allogeneic hematopoietic stem cell transplantation (HSCT) from a human leukocyte antigen-matched unrelated donor for myelodysplastic syndrome. No exacerbation of hypersensitivity pneumonitis was observed after HSCT. An environmental inhalation challenge test involving exposure to his bar confirmed the remission of hypersensitivity pneumonitis after HSCT. This case demonstrates that hypersensitivity pneumonitis can be remitted by HSCT.

Feasibility of continued treatment with dupilumab in patients with type 2 inflammatory disease who developed eosinophilic pneumonia: 3 case reports.

Several reports have described dupilumab-induced eosinophilic pneumonia (EP) after treatment with dupilumab in patients with type 2 inflammatory disease. Other reports have suggested the efficacy of dupilumab for chronic EP (CEP). Whether dupilumab can be continued in patients with type 2 inflammatory disease who develop EP during dupilumab treatment remains unclear. We present herein three cases with different clinical presentations involving dupilumab and EP. In Case 1, dupilumab was discontinued because of dupilumab-induced EP during the treatment of asthma. In Case 2, although pre-existing idiopathic EP worsened during the treatment of eosinophilic chronic rhinosinusitis (ECRS), dupilumab was continued. In Case 3, CEP and ECRS were successfully treated with dupilumab and corticosteroids were discontinued. In conclusion, treatment with dupilumab in patients with type 2 inflammatory disease and idiopathic EP is worth considering if the benefits are deemed to outweigh the risks and careful attention is given to the clinical course.

Frequency and clinical features of radiographic head injury caused by inpatient falls: a single-centre retrospective cohort study.

OBJECTIVES: The lack of clear criteria makes it difficult for clinicians to determine which patients should be imaged after an inpatient fall. This study identified the clinical characteristics of patients who required a head CT scan following an inpatient fall. DESIGN: This was a retrospective cohort study conducted from January 2016 to December 2018. We obtained the data from our safety surveillance database, which record all cases of inpatient falls in our hospital. SETTING: Single-centre, tertiary, secondary care hospital. PARTICIPANTS: We included all consecutive patients who claimed to have fallen and bruised their heads as well as patients who were confirmed to have a bruise on the head but were unavailable to be interviewed about the fall. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was radiographic head injury revealed on head CT after a fall. RESULTS: Overall, 834 adult patients (662 confirmed and 172 suspected cases) were included. The median age was 76 years, and 62% were men. Patients with radiographic head injury were more likely to have a lower platelet count, consciousness disturbance and new vomiting episodes compared with those without radiographic head injury (all p<0.05). The use of anticoagulants or antiplatelets was not different between patients with and without radiographic head injury. Among the 15 (1.8%) patients with a radiographic head injury, 13 with intracranial haemorrhage had at least one of the following characteristics: received anticoagulant or antiplatelet agents, platelet count of <2.0×109/L, consciousness disturbance or new vomiting episodes. There were no deaths among patients with radiographic head injuries. CONCLUSIONS: The incidence of radiographic head injury due to falls in adult inpatients with suspected or confirmed head injuries was 1.8%. Only patients with risk factors had radiographic head injuries, which might help reduce the number of unnecessary CT scans in inpatient falls. TRIAL REGISTRATION NUMBER: Study protocol (Kurashiki Central Hospital, Medical ethical committee. IRB no. 3750).

Home High-Flow Nasal Cannula Oxygen Therapy for Stable Hypercapnic COPD: A Randomized Clinical Trial.

Rationale: The long-term effects of using a high-flow nasal cannula for chronic hypercapnic respiratory failure caused by chronic obstructive pulmonary disease remain unclear. Objectives: To assess whether long-term high-flow nasal cannula use reduces the number of exacerbations and improves other physiological parameters in patients with chronic hypercapnic respiratory failure caused by chronic obstructive pulmonary disease. Methods: We enrolled 104 participants (aged ⩾40 yr) with daytime hypercapnia (Global Initiative for Chronic Obstructive Lung Disease stages 2-4) receiving long-term oxygen therapy (⩾16 h/d for ⩾1 mo) and randomly assigned them to high-flow nasal cannula/long-term oxygen therapy and long-term oxygen therapy groups. The primary endpoint was the moderate or severe exacerbation rate. We compared changes from baseline in arterial blood gas values, peripheral oxygen saturation, pulmonary function, health-related quality-of-life scores, and the 6-minute-walk test. Measurements and Main Results: High-flow nasal cannula use significantly reduced the rate of moderate/severe exacerbations (unadjusted mean count 1.0 vs. 2.5, a ratio of the adjusted mean count between groups [95% confidence interval] of 2.85 [1.48-5.47]) and prolonged the duration without moderate or severe exacerbations. The median time to first moderate or severe exacerbation in the long-term oxygen therapy group was 25 (14.1-47.4) weeks; this was not reached in the high-flow nasal cannula/long-term oxygen therapy group. High-flow nasal cannula use significantly improved health-related quality of life scores, peripheral oxygen saturation, and specific pulmonary function parameters. No safety concerns were identified. Conclusions: A high-flow nasal cannula is a reasonable therapeutic option for patients with stable hypercapnic chronic obstructive pulmonary disease and a history of exacerbations. Clinical trial registered with www.umin/ac.jp (UMIN000028581) and www.clinicaltrials.gov (NCT03282019).

Essential role of IL-23 in the development of acute exacerbation of pulmonary fibrosis.

Acute exacerbation of idiopathic pulmonary fibrosis has a poor prognosis associated with neutrophilic inflammation. Interleukin-23 is a proinflammatory cytokine involved in neutrophilic inflammation. However, little is known about its role in acute exacerbation of pulmonary fibrosis. This study was performed to determine the role of interleukin-23 in acute exacerbation of pulmonary fibrosis. For assessment of acute exacerbation of pulmonary fibrosis, mice were intratracheally administered bleomycin followed by lipopolysaccharide. Inflammatory cells, cytokine levels, and morphological morphometry of the lungs were analyzed. Cytokine levels were measured in the bronchoalveolar lavage fluid of idiopathic pulmonary fibrosis patients with or without acute exacerbation. Interleukin-23, -17A, and -22 levels were increased in the airway of mice with acute exacerbation of pulmonary fibrosis. Interleukin-23p19-deficient mice with acute exacerbation of pulmonary fibrosis had markedly reduced airway inflammation and fibrosis associated with decreased levels of interleukin-17A and -22 compared with wild-type mice. Treatment with an anti-interleukin-23 antibody attenuated airway inflammation and fibrosis and reduced interleukin-17A and -22 levels in mice with acute exacerbation of pulmonary fibrosis. T-helper type 17 cells were the predominant source of interleukin-17A in mice with acute exacerbation of pulmonary fibrosis. Interleukin-23 levels in bronchoalveolar lavage fluid tended to be higher in idiopathic pulmonary fibrosis patients with than without acute exacerbation. The data presented here suggest that interleukin-23 is essential for the development of acute exacerbation of pulmonary fibrosis and that blockade of interleukin-23 may be a new therapeutic strategy for acute exacerbation of pulmonary fibrosis.

Usefulness of ß-lactam and macrolide combination therapy for treating community-acquired pneumonia patients hospitalized in the intensive care unit: Propensity score analysis of a prospective cohort study.

INTRODUCTION: Whether ß-lactam and macrolide combination therapy reduces mortality in severe community-acquired pneumonia (SCAP) patients hospitalized in the intensive care unit (ICU) is controversial. The aim of the present study was to evaluate the usefulness of ß-lactam and macrolide combination therapy for SCAP patients hospitalized in the ICU. METHODS: A prospective, observational, cohort study of hospitalized pneumonia patients was performed. Hospitalized SCAP patients admitted to the ICU within 24 h between October 2010 and October 2017 were included for analysis. The primary outcome was 30-day mortality, and secondary outcomes were 14-day mortality and ICU mortality. Inverse probability of treatment weighting (IPTW) analysis as a propensity score analysis was used to reduce biases, including six covariates: age, sex, C-reactive protein, albumin, Pneumonia Severity Index score, and APACHE II score. RESULTS: A total of 78 patients were included, with 48 patients in the non-macrolide-containing ß-lactam therapy group and 30 patients in the macrolide combination therapy group. ß-lactam and macrolide combination therapy significantly decreased 30-day mortality (16.7% vs. 43.8%; P = 0.015) and 14-day mortality (6.7% vs. 31.3%; P = 0.020), but not ICU mortality (10% vs 27.1%, P = 0.08) compared with non-macrolide-containing ß-lactam therapy. After adjusting by IPTW, macrolide combination therapy also decreased 30-day mortality (odds ratio, 0.29; 95%CI, 0.09-0.96; P = 0.04) and 14-day mortality (odds ratio, 0.19; 95%CI, 0.04-0.92; P = 0.04), but not ICU mortality (odds ratio, 0.34; 95%CI, 0.08-1.36; P = 0.13). CONCLUSIONS: Combination therapy with ß-lactam and macrolides significantly improved the prognosis of SCAP patients hospitalized in the ICU compared with a non-macrolide-containing ß-lactam regimen.

Impact of bronchoalveolar lavage lymphocytosis on the effects of anti-inflammatory therapy in idiopathic non-specific interstitial pneumonia, idiopathic pleuroparenchymal fibroelastosis, and unclassifiable idiopathic interstitial pneumonia.

BACKGROUND: Idiopathic non-specific interstitial pneumonia (iNSIP), idiopathic pleuroparenchymal fibroelastosis (iPPFE), and unclassifiable idiopathic interstitial pneumonia (IIP) are IIPs with chronic fibrotic phenotypes, and unlike idiopathic pulmonary fibrosis, they have often been treated with anti-inflammatory drugs, including corticosteroids and immunosuppressants. However, the impact of bronchoalveolar lavage (BAL) lymphocytosis on the effects of anti-inflammatory therapy has never been evaluated. This study aimed to elucidate whether BAL lymphocytosis can be used to predict the efficacy of anti-inflammatory drugs for iNSIP, iPPFE, and unclassifiable IIP. METHODS: Japanese patients diagnosed with iNSIP, iPPFE, and unclassifiable IIP by multidisciplinary discussion were identified using the nationwide registry. Eligible patients were stratified into four groups with and without BAL lymphocytosis and anti-inflammatory therapy to compare overall survival (OS) and changes in lung function. BAL lymphocytosis was defined as a lymphocyte differential count > 15%, and the cut-off was corroborated by survival classification and regression tree analysis. RESULTS: Overall, 186 patients (37 iNSIP, 16 iPPFE, and 133 unclassifiable IIP) were analyzed. Limited to patients treated with anti-inflammatory drugs (n = 123), patients with BAL lymphocytosis had a better prognosis [hazard ratio (HR), 0.26; 95% confidence interval (CI), 0.11-0.63; P = 0.003], higher slope of forced vital capacity (FVC) % predicted for 2 years, and longer OS (log-rank test, P = 0.012) than those without BAL lymphocytosis. On multivariate analysis, BAL lymphocytosis (HR 0.31; 95% CI 0.13-0.75; P = 0.009) was a prognostic factor for OS, along with age and FVC % predicted. Conversely, for patients managed without anti-inflammatory therapy (n = 63), the presence or absence of BAL lymphocytosis had no prognostic value. CONCLUSIONS: BAL lymphocytosis is associated with good outcomes in patients treated with anti-inflammatory drugs, but has no prognostic value when anti-inflammatory drugs are not used. BAL lymphocytosis may provide a predictive biomarker for identifying patients with iNSIP, iPPFE and unclassifiable IIP who are likely to benefit from anti-inflammatory drugs.

Acute Pulmonary Graft-Versus-Host Disease in a Patient with Adult T-cell Leukemia-Lymphoma Diagnosed by a Cryobiopsy.

A 51-year-old woman with adult T-cell leukemia-lymphoma was hospitalized in order to undergo allogeneic hematopoietic stem-cell transplantation. On day 29 after transplantation, she began to experience hypoxia upon exertion. Chest computed tomography revealed centrilobular granular shadows, and pulmonary function tests revealed a remarkable obstructive ventilatory impairment compared to before transplantation. A histopathological analysis following a transbronchial lung cryobiopsy revealed acute graft-versus-host disease (GVHD). We herein report a rare case of histopathologically diagnosed acute pulmonary GVHD with spontaneous remission.

Acute onset systemic lupus erythematosus interstitial lung disease: A case report.

A 40-year-old Japanese man was diagnosed with systemic lupus erythematosus. Chest computed tomography showed patchy consolidation in both lungs. A cryobiopsy and bronchoalveolar lavage showed organizing pneumonia, not acute lupus pneumonia or diffuse alveolar hemorrhage. This case demonstrates the usefulness of cryobiopsy for the management of systemic lupus erythematosus interstitial lung disease.

Extracorporeal membrane oxygenation in Stenotrophomonas maltophilia pneumonia during acute myeloid leukemia: A case report.

Stenotrophomonas maltophilia (S. maltophilia) is a Gram-negative, multidrug-resistant organism that both opportunistically infects the bloodstream and leads to pneumonia in immunosuppressed patients, including those with hematologic malignancies. In patients with severe respiratory failure, venovenous extracorporeal membrane oxygenation (VV ECMO) can stabilize the respiratory status. However, whether ECMO in patients with hematologic malignancies improves the clinical outcomes is still controversial because ECMO increases the risk of the exacerbation of sepsis and bleeding. We report a case of a 46-year-old man with Stenotrophomonas maltophilia hemorrhagic pneumonia acquired during consolidation chemotherapy for acute myeloid leukemia in whom VV ECMO lead to a good clinical outcome. The stabilization of his respiratory status achieved with VV ECMO allowed time for trimethoprim-sulfamethoxazole antibiotic therapy to improve the pneumonia. We suggest the background of patients, including comorbidities and general conditions, should be taken into account when considering the clinical indications of ECMO.

Therapeutic plasma exchange for clinically amyopathic dermatomyositis (CADM) associated with rapidly progressive interstitial pneumonia.

BACKGROUND: Patients with clinically amyopathic dermatomyositis (CADM) with anti-melanoma differentiation-associated gene 5 antibody (anti-MDA5 Ab) frequently develop rapidly progressive interstitial pneumonia (RPIP), often with fatal outcomes. Therapeutic plasma exchange (TPE) has been reported as effective against CADM-RPIP refractory to conventional immunosuppressive therapy. However, the detailed mechanisms by which TPE improves disease activity of CADM-RPIP remain unclear. AIM: To elucidate the clinical and demographic characteristics of patients with anti-MDA5 Ab-positive CADM-RPIP treated with TPE and to analyze changes in laboratory findings before, during, and after TPE. MATERIALS & METHODS: Patients hospitalized for CADM-RPIP and treated with TPE in 2017 and 2018 were analyzed retrospectively. RESULTS: Three patients were successfully treated with TPE, with good tolerance. Anti-MDA5 Ab titers decreased significantly over the course of TPE. CONCLUSION: We emphasize that TPE could represent an effective treatment option for CADM-RPIP refractory to traditional therapy. Removal of anti-MDA5 Ab and other pathogenic factors may facilitate favorable outcomes.

Radiological fibrosis score is strongly associated with worse survival in rheumatoid arthritis-related interstitial lung disease.

OBJECTIVES: High-resolution computed tomography (HRCT) parenchymal patterns have been used to predict prognosis in patients with interstitial lung disease (ILD). In idiopathic pulmonary fibrosis, the fibrosis score (i.e. the combined extent of reticulation and honeycombing) has been associated with worse survival. This study aimed to identify HRCT patterns and patient characteristics that can predict poor prognosis in rheumatoid arthritis-related ILD (RA-ILD). METHODS: We retrospectively analysed 65 patients with newly diagnosed RA-ILD from 2007 to 2016 at Kurashiki Central hospital. Using univariate and bivariate Cox regression analysis, associations with mortality, were identified. RESULTS: During a median follow-up of 56.5 months, 16/65 (24.6%) patients died. Univariate analysis identified six significant poor prognostic factors: lower baseline % predicted forced vital capacity, total interstitial disease score, reticulation score, traction bronchiectasis score, fibrosis score, and definite UIP pattern. Fibrosis score remained to be an independently significant poor prognostic factor of survival on bivariate analysis. Patients with a fibrosis score >20% had higher mortality (HR, 9.019; 95% CI, 2.87-28.35; p < .05). CONCLUSION: This study showed that fibrosis score is strongly associated with worse survival in RA-ILD, and patients with fibrosis score >20% had a 9.019-fold increased risk of mortality.

Heat-not-burn cigarettes induce fulminant acute eosinophilic pneumonia requiring extracorporeal membrane oxygenation.

BACKGROUND: Although the cause of acute eosinophilic pneumonia (AEP) has not yet been fully clarified, cigarette smoking is reported to be a risk factor for developing AEP. The heat-not-burn cigarette (HNBC) was developed to reduce the adverse effects of smoke on the user's surroundings. However, the health risks associated with HNBCs have not yet been clarified. We report a successfully treated case of fatal AEP presumably induced by HNBC use. PRESENTATION OF CASE: A 16-year-old man commenced HNBC smoking two weeks before admission and subsequently suffered from shortness of breath that gradually worsened. The patient was transferred to emergency department and immediately intubated because of respiratory failure. Computed tomography showed mosaic ground-glass shadows on the distal side of both lungs with a PaO2/FIO2 ratio of 76. The patient required veno-venous extracorporeal membrane oxygenation (ECMO) for severe respiratory failure. He was diagnosed with AEP by clinical course and detection of eosinophils in sputum; thus, methylprednisolone was administrated. The patient was weaned off ECMO four days after initiation and extubated the day after. He fully recovered without sequelae. CONCLUSION: As far as we know, our patient is the first case of AEP induced by HNBC use successfully treated with ECMO. Emergency physicians must be aware that HNBCs can induce fatal AEP.

Traction bronchiectasis on high-resolution computed tomography may predict fatal acute eosinophilic pneumonia.

BACKGROUND: Most patients with acute eosinophilic pneumonia (AEP) show rapid improvement. However, some cases of AEP prove fatal. The aims of this study were to determine the clinical, radiographic, and pathologic characteristics of patients in whom AEP has a fatal outcome and to identify predictors of a poor prognosis. METHODS: We retrospectively identified the medical records of all patients diagnosed with AEP at our institution in Japan from July 2005 to July 2013. RESULTS: There were four deaths among 41 patients diagnosed to have AEP during the study period. All the patients who died were male; three cases were idiopathic and one was medication-related. The median bronchoalveolar lavage eosinophil differential count was 59%. An autopsy was performed on the patient with medication-related AEP who died and the pathologic finding was diffuse alveolar damage with eosinophilic infiltration. Diffuse ground-glass attenuation and traction bronchiectasis (TBE) were identified on high-resolution computed tomography in the four patients with fatal AEP. TBE was observed in six patients (five with idiopathic AEP, one with medication-related AEP), and 67% of these patients died. None of the patients with smoking-related AEP had TBE; all these patients had better responses to treatment and survived. CONCLUSIONS: We observed the characteristics of patients with fatal AEP who did not respond to treatment. TBE was observed in all fatal cases and may be associated with a poor prognosis.

The prognostic performance of qSOFA for community-acquired pneumonia.

BACKGROUND: Quick Sepsis-related Organ Failure Assessment (qSOFA) is a new screening system for sepsis. The prognostic performance of qSOFA for patients with suspected infections outside the intensive care unit (ICU) is similar to that of full SOFA; however, its performance for community-acquired pneumonia (CAP) has not yet been evaluated in detail.The objectives of the present study were to compare the prognostic performance of qSOFA with existing pneumonia severity scores, such as CURB-65 (confusion, blood urea nitrogen > 19 mg/dL, respiratory rate ≥ 30/min, systolic blood pressure < 90 mmHg, or diastolic blood pressure ≤ 60 mmHg, age ≥ 65 years) and the pneumonia severity index (PSI), and examine its usefulness for predicting mortality and ICU admission in patients with CAP of high severity and mortality that requires hospitalization. METHODS: We performed a secondary analysis of data from a prospective observational study of adult patients who were admitted to our hospital between October 2010 and June 2016. We compared the prognostic performance of qSOFA, CURB-65, and PSI for predicting in-hospital mortality and ICU admission using the C statistics. RESULTS: The median age of the 1045 enrolled patients was 77 (68-83) years, and 71.4% were males. The in-hospital mortality and ICU admission rates of the entire cohort were 6.1 and 7.9%, respectively. All scores were significantly higher in non-survivors and ICU admission patients than in survivors and non-ICU admission patients (p < 0.001). The C statistics of qSOFA for predicting in-hospital mortality was 0.69 (95% CI 0.63-0.75), and no significant differences were observed between CURB-65 (C statistics, 0.75; 95% CI 0.69-0.81) and PSI (C statistics, 0.74; 95% CI 0.69-0.80). The C statistics of qSOFA for predicting ICU admission was 0.76 (95% CI 0.71-0.80), and no significant differences were noted between CURB-65 (C statistics, 0.73; 95% CI 0.67-0.79) and PSI (C statistics, 0.72; 95% CI 0.66-0.78). CONCLUSIONS: Regarding hospitalized CAP, the prognostic performance of qSOFA for in-hospital mortality and ICU admission was not significantly different from those of CURB-65 and PSI. qSOFA only requires a few items and vital signs, and, thus, may be particularly useful for emergency department or non-respiratory specialists.

Radiographic fibrosis score predicts survival in systemic sclerosis-associated interstitial lung disease.

BACKGROUND AND OBJECTIVE: Interstitial lung disease (ILD) is a common pulmonary manifestation of systemic sclerosis (SSc). It is unknown whether radiographic fibrosis score predicts mortality in SSc-associated ILD (SSc-ILD). We retrospectively analysed patients with SSc-ILD to evaluate whether radiographic fibrosis score was a useful predictor of mortality. METHODS: We identified SSc-ILD patients evaluated at Kurashiki Central Hospital (Japan) from 2006 to 2016, and radiographic fibrosis scores based on the extent of reticulation and honeycombing on high-resolution computed tomography (HRCT) scanning were calculated by manually tracing around each fibrotic area. Independent predictors of overall survival were determined using the Cox proportional hazards model. RESULTS: The study included 48 patients, of whom 19 had usual interstitial pneumonia on HRCT. The median follow-up period was 56.6 months, and over the follow-up period 15 patients died. The 5-year survival was 72.4%. In the multivariate analysis, radiographic fibrosis score, age, being male and forced vital capacity were independently associated with an increased risk of death, while HRCT pattern was not. CONCLUSION: A high radiographic fibrosis score was a poor prognostic factor in SSc-ILD. More widespread fibrosis was associated with an increased risk of death, independent of HRCT pattern.

Cyclosporin A in idiopathic chronic fibrosing interstitial pneumonia without idiopathic pulmonary fibrosis.

BACKGROUND: We have sometimes observed interstitial pneumonia which had chronic course and unknown causes but not diagnosed as idiopathic pulmonary fibrosis (IPF). However, the treatment strategy was not established definitely. To clarify the usefulness of cyclosporin A (CsA) in idiopathic chronic fibrosing interstitial pneumonia (iCFIP) without IPF, we examined longitudinal changes in pulmonary physiology. METHODS: Japanese patients with iCFIP without IPF treated with CsA were identified retrospectively. Linear mixed-effects models were used to evaluate changes in pulmonary physiology after adjusting for age, sex, and smoking history. Primary outcomes were longitudinal trajectories of the percent predicted forced vital capacity (%FVC), percent predicted diffusing capacity for carbon monoxide (%DLco), and composite physiologic index (CPI) before and after CsA. RESULTS: Thirty-three patients were included. Before CsA initiation, %FVC, %DLco, and CPI declined at rates of 9.1%, 8.6% and -7.1 per 1 year, respectively. After CsA initiation, the gradient of %FVC showed significant improvements in 0-1 years (6.2%±3.0%; P<0.01) and in 1-2 years (10.0%±3.6%; P<0.01); %DLco improved in 0-1 year (4.0%±4.6%; P=0.09) and in 1-2 years (7.0%±5.6%; P=0.02); and CPI improved in 0-1 year (3.2%±3.3%; P=0.06) and in 1-2 years (4.6%±4.1%; P=0.03). CONCLUSIONS: CsA for iCFIP without IPF may be associated with improvements in pulmonary physiology in 2 years. Further studies are needed to determine the role of CsA in iCFIP without IPF.

Domiciliary High-Flow Nasal Cannula Oxygen Therapy for Patients with Stable Hypercapnic Chronic Obstructive Pulmonary Disease. A Multicenter Randomized Crossover Trial.

RATIONALE: A growing evidence base suggests a benefit of using high-flow nasal cannula oxygen therapy in the acute setting. However, the clinical benefit of domiciliary use of high-flow nasal cannula oxygen therapy in patients with chronic hypercapnic respiratory failure due to chronic obstructive pulmonary disease remains unclear. OBJECTIVES: To evaluate the efficacy and safety of high-flow nasal cannula oxygen therapy use in patients with stable chronic obstructive pulmonary disease. METHODS: We conducted a multicenter, randomized crossover trial comparing high-flow nasal cannula oxygen therapy plus long-term oxygen therapy with long-term oxygen therapy only in 32 adults with stable hypercapnic chronic obstructive pulmonary disease. Participants were randomized to receive either 6 weeks of high-flow nasal cannula oxygen therapy/long-term oxygen therapy using the myAIRVO 2 device followed by another 6 weeks of long-term oxygen therapy only or long-term oxygen therapy only followed by high-flow nasal cannula oxygen therapy/long-term oxygen therapy. The primary outcome was the change in quality of life as assessed by St. George's Respiratory Questionnaire for chronic obstructive pulmonary disease. A linear mixed-effects model was used to account for treatment effect, time effect, allocation effect, and participant effect. RESULTS: Of 32 study participants, 29 completed the study. At the end of 12 weeks, high-flow nasal cannula oxygen therapy/long-term oxygen therapy treatment improved the mean total St. George's Respiratory Questionnaire for chronic obstructive pulmonary disease score compared with long-term oxygen therapy only (7.8 points; 95% confidence interval, 3.7 to 11.9; P < 0.01). Similarly, high-flow nasal cannula oxygen therapy/long-term oxygen therapy treatment improved the arterial partial pressure of carbon dioxide (adjusted treatment effect, -4.1 mm Hg; 95% confidence interval, -6.5 to -1.7 mm Hg), pH (adjusted treatment effect, +0.02; 95% confidence interval, 0.01 to 0.02), and median nocturnal transcutaneous carbon dioxide pressure (adjusted treatment effect, -5.1 mm Hg; 95% confidence interval, -8.4 to -1.8 mm Hg). High-flow nasal cannula oxygen therapy/long-term oxygen therapy treatment did not improve the arterial partial pressure of oxygen, dyspnea, spirometry, lung volume, 6-minute walk test, or physical activity. The most frequent high-flow nasal cannula oxygen therapy-related adverse event encountered was nocturnal sweating (n = 6 [20.7%]). Four severe adverse events occurred (two in each group) and were deemed unrelated to the intervention. CONCLUSIONS: Six weeks of treatment with high-flow nasal cannula oxygen therapy improved health-related quality of life and reduced hypercapnia in patients with stable hypercapnic chronic obstructive pulmonary disease. Clinical trial registered with www.clinicaltrials.gov (NCT02545855) and www.umin/ac.jp (UMIN000017639).

Diffuse Alveolar Hemorrhage in IgA Vasculitis with an Atypical Presentation.

IgA vasculitis (IgAV) commonly occurs in young children, who present with a tetrad of purpura, abdominal pain, arthralgia and nephritis. Diffuse alveolar hemorrhage (DAH) is a rare complication of IgAV. We herein report an adult case of IgAV with a presentation of DAH and nephritis (pulmonary renal syndrome, PRS), but without other typical manifestations, such as purpura, abdominal pain and arthralgia. A 33-year-old man presented with hemoptysis and a low-grade fever and was diagnosed to have IgAV based on the results of a renal biopsy. Treatment with corticosteroids, cyclophosphamide, and plasmapheresis was effective. IgAV should therefore be considered in the differential diagnosis of adult PRS.