Noninfectious Pulmonary Complications Research Articles

Pulmonary Complications After Solid Organ Transplantation: An Autopsy Perspective

Pulmonary complications following solid organ transplantation are common and often infectious in nature. Articles describing noninfectious pulmonary complications overwhelmingly rely on clinical and radiographic data. There are a limited number of studies with companion histology delineating the clinical diagnoses of pulmonary complications. This contrasts with blood and bone marrow transplantations. Using a retrospective cohort approach, the current study aimed to assess antemortem and postmortem pulmonary findings in solid organ transplantation recipients. Medical records and autopsy materials from 92 solid organ transplantation recipients were reviewed. Pulmonary complications were identified in 70 patients (76%). For patients with pulmonary complications at autopsy the mean survival posttransplantation was 3.48 years as compared to 7.29 years for patients without pulmonary complications at autopsy (P = .01). Twenty-eight infectious complications (fungal pneumonia, n = 20; cytomegalovirus pneumonia, n = 7; bacterial pneumonia, n = 1) and 113 noninfectious pulmonary complications were identified. The most common noninfectious findings were diffuse alveolar damage (n = 32), organizing pneumonia (n = 31), and pulmonary thromboemboli (n = 26). Disseminated infections and respiratory failure were the most common immediate causes of death (n = 24 and n = 23, respectively). Most noninfectious complications were not diagnosed antemortem.

Clinical significance of radiological pleuroparenchymal fibroelastosis pattern in interstitial lung disease patients registered for lung transplantation: a retrospective cohort study

BackgroundRadiological pleuroparenchymal fibroelastosis (PPFE) lesion is characterized by pleural thickening with associated signs of subpleural fibrosis on high-resolution computed tomography (HRCT). This study evaluated the clinical significance of radiological PPFE as an isolated finding or associated with other interstitial lung diseases (ILDs) in patients having fibrotic ILDs and registered for cadaveric lung transplantation (LT).MethodsThis retrospective study included 118 fibrotic ILD patients registered for LT. Radiological PPFE on HRCT was assessed. The impact of radiological PPFE on clinical features and transplantation-censored survival were evaluated.ResultsRadiological PPFE was observed in 30/118 cases (25%): definite PPFE (PPFE concentrated in the upper lobes, with involvement of lower lobes being less marked) in 12 (10%) and consistent PPFE (PPFE not concentrated in the upper lobes, or PPFE with features of coexistent disease present elsewhere) in 18 (15%). Of these, 12 had late-onset non-infectious pulmonary complications after hematopoietic stem-cell transplantation and/or chemotherapy (LONIPCs), 9 idiopathic PPFE, and 9 other fibrotic ILDs (idiopathic pulmonary fibrosis, IPF; other idiopathic interstitial pneumonias, other IIPs; connective tissue disease-associated ILD, CTD-ILD, and hypersensitivity pneumonia, HP). Radiological PPFE was associated with previous history of pneumothorax, lower body mass index, lower percentage of predicted forced vital capacity (%FVC), higher percentage of predicted diffusion capacity of carbon monoxide, less desaturation on six-minute walk test, and hypercapnia. The median survival time of all study cases was 449 days. Thirty-seven (28%) received LTs: cadaveric in 31 and living-donor lobar in six. Of 93 patients who did not receive LT, 66 (71%) died. Radiological PPFE was marginally associated with better survival after adjustment for age, sex, %FVC, and six-minute walk distance < 250 m (hazard ratio 0.51 [0.25–1.05], p = 0.07). After adjustment for covariates, idiopathic PPFE and LONIPC with radiological PPFE was associated with better survival than fibrotic ILDs without radiological PPFE (hazard ratio 0.38 [0.16–0.90], p = 0.03), and marginally better survival than other fibrotic ILDs with radiological PPFE (hazard ratio, 0.20 [0.04–1.11], p = 0.07).Conclusionsidiopathic PPFE and LONIPC with radiological PPFE has better survival on the wait list for LT than fibrotic ILDs without radiological PPFE, after adjustment for age, sex, %FVC, and six-minute walk distance.

Lung histopathology of non-infectious pulmonary complications after allogeneic haematopoietic stem cell transplantation.

Non-infectious pulmonary complications (NIPCs) occur frequently following allogeneic haematopoietic stem cell transplantation (HSCT). As there is no consensus on the description of the related pulmonary pathological lesions, pathologist reports and clinical conclusions are largely inconsistent in routine practice. The aim of our study was to provide an accurate overview of post-allogeneic HSCT NIPCs from a large number of lung biopsies. We reviewed 61 lung biopsies in patients with an NIPC, including 51 surgical lung biopsies, four post-mortem biopsies and six lung explants. We found both bronchiolar (n = 59) and alveolar/interstitial pathologies (n = 27). We describe two types of bronchiolar lesions: bronchiolectasies (n = 37) and fibrous and cellular lesions with luminal narrowing (n = 43). We found a wide spectrum of airway/interstitial pathologies that were labelled using the terminology of the 2013 American Thoracic Society and European Respiratory Society (ATS/ERS) classification of idiopathic interstitial pneumonias (IIPs), including the following: organising pneumonia (OP, n = 8), non-specific interstitial pneumonia (NSIP, n = 9), diffuse alveolar damage (DAD, n = 6), lymphoid interstitial pneumonia (LIP, n = 1) and pleuroparenchymal fibroelastosis (PPFE, n = 2), as well as one instance of associated PPFE and NSIP. Interstitial pathology was associated with bronchiolar lesions in 41% of the cases reviewed (n = 25). Lung airway and interstitial inflammation was still present in lung explants from patients who underwent lung transplantation for post-allogeneic HSCT end-stage respiratory insufficiency. Herein, we describe a wide spectrum of pathological lung lesions encountered in post-allogeneic HSCT NIPCs.

Whole-Body Lung Function Test–Derived Outcome Predictors in Allogenic Stem Cell Transplantation

Despite clinical advances, late onset pulmonary complications in adult recipients of allogenic stem cell transplantation are a major cause of morbidity and mortality. Reported incidence and risk factors in the literature vary broadly and are partly contradictory. Identification of pretransplant factors associated with major complications would be helpful to define individual treatment strategies and early initiation of preventive measures.To evaluate incidence and risk factors of late onset noninfectious pulmonary complications, with special regard to small airways disease (SAD) and bronchiolitis obliterans syndrome (BOS), indicating graft-versus-host disease, following myeloablative versus nonmyeloablative allogenic stem cell transplantation.We reviewed the clinical records and assessed the course of lung function and pulmonary complications in adults who underwent allogenic stem cell transplantation for hematological malignancies between 1999 and 2015 using nonmyeloablative (n = 179) or myeloablative (n = 130) conditioning at the Division of Hematology of the Medical University of Graz. All patients underwent body plethysmography pulmonary function test (PFT), diffusion capacity for carbon monoxide, and arterial blood gas analysis before and repeatedly after transplant. SAD was defined as maximal expiratory flow at 50% and 25% of forced vital capacity <70% predicted.Ventilatory disorders and gas transfer abnormalities were common before and after allogenic stem cell transplantation, independent of conditioning regimen. SAD was common in the nonmyeloablative (34%) and myeloablative (29%) groups. The 100-day post-transplant mortality was significantly associated with reduced pretransplant total lung capacity <80%. Mortality 100 days post-transplant was significantly associated with pretransplant SAD and a pretransplant smoking history. In this subset, a smoking history was independently associated with increased mortality, with a 5-year mortality of 45% compared with 26% in never-smokers. Pretransplant SAD was not predictive for the later development of BOS.Smoking history, pretransplant restrictive PFT, and pre-existing SAD are important risk factors for death following allogenic stem cell transplantation. However, pretransplant SAD is not a predictor of long-term complications, including BOS.

Noninfectious lung complications after allogeneic haematopoietic stem cell transplantation.

Epidemiological data on late-onset noninfectious pulmonary complications (LONIPCs) following allogeneic haematopoietic stem cell transplantation (HSCT) are derived exclusively from retrospective studies and are conflicting. We aimed to evaluate prospectively the incidence, risk factors and outcomes for LONIPCs.All consecutive patients scheduled to receive allogeneic HSCT between 2006 and 2008 at a university teaching hospital in France were screened for inclusion in the study. Eligible patients were those surviving at day 100. Among 243 screened patients, 198 patients were included in the analysis. The median (interquartile range) follow-up was 72.3 (15.2-88.5) months. 55 LONIPCs were diagnosed in 43 patients. Bronchiolitis obliterans syndrome (n=22) and interstitial lung disease (n=12) were the most common LONIPCs. At 36 months after inclusion, the estimated cumulative incidence of LONIPCs was 19.8% (95% CI 14.2-25.3%). The estimated median survival after the diagnosis of LONIPCs was 78.5 months (95% CI 20.0-not reached). Based on a multivariate Cox model, a history of chest irradiation anytime prior to HSCT, a history of pneumonia within 100 days post-HSCT and a low mean forced expiratory flow at 25-75% of forced vital capacity at day 100 were associated with the development of LONIPCs.Our data provide clues to identify patients at high risk of developing LONIPCs. These patients should be targeted for close monitoring to provide earlier LONIPC treatment or prophylactic treatment.

RISK OF DEVELOPING ACTIVE TB IN IBD PATIENTS TREATED WITH ATNI-TNF

AIM. To develop an investigation complex for IBD-patients with the anti-TNF therapy to decrease the risk of active TB. METHODS. In Moscow Research and Clinical Center for TB Control 454 patients with IBD were screened prior to initiation of anti-TNF treatment and 167 (36,8%) of them - during the anti-TNF therapy. Tuberculin skin test (TST) and chest radiography were used for screening and evaluation of pulmonary adverse effects (every 6 months and additionally in cases of any respiratory signs). RESULTS. Of 454 patients investigated during screening X-ray, chest radiography findings were detected in 29 (6,4%), which required additional investigation, among them in 14 patients, findings considered as residual TB lesions. In the other 15 patients, the radiographic findings caused by previous non-specific pulmonary infections. Positive TST implicates preventive antituberculosis therapy, which was provided 37 patients (before and under anti-TNF therapy). During provided to 167 patients the anti-TNF therapy, were developed pulmonary adverse effects: 10 incidences of active TB lung infection 3 case of sarcoidosis, 1 case of fibrosing alveolitis, and two case of non-CONCLUSION. The patients with IBD, treated by anti-TNF therapy, have a risk of development of a wide variety of infectious and non-infectious pulmonary complications, including TB. It is therefore highly important to carefully monitor the patients prior and during the anti-TNF therapy (every 6 months) for a timely detection of pulmonary conditions potentially associated with the treatment.

Current Approach to Non-Infectious Pulmonary Complications of Hematopoietic Stem Cell Transplantation.

Hematopoietic stem cell transplantation is an established treatment for patients with a wide range of malignant and nonmalignant conditions. Noninfectious pulmonary complications still remain a leading cause of morbidity and mortality in these patients. Treating hematopoietic stem cell transplantation recipients with noninfectious pulmonary complications is still challenging, and the current treatment armamentarium and strategies are not adequate for patients receiving hematopoietic stem cell transplantation. Further trials are needed for a better description of the pathogenesis and the complete diagnostic criteria as well as for the development of effective therapeutic approaches for the management of noninfectious pulmonary complications of the hematopoietic stem cell transplantation. This review outlines the incidence, risk factors, pathogenesis, and clinical spectrum and discusses the current approaches to the management of noninfectious pulmonary complications of Hematopoietic stem cell transplantation.

Lung transplantation after allogeneic stem cell transplantation: a pan-European experience.

Late-onset noninfectious pulmonary complications (LONIPCs) affect 6% of allogeneic stem cell transplantation (SCT) recipients within 5 years, conferring subsequent 5-year survival of 50%. Lung transplantation is rarely performed in this setting due to concomitant extrapulmonary morbidity, excessive immunosuppression and concerns about recurring malignancy being considered contraindications. This study assesses survival in highly selected patients undergoing lung transplantation for LONIPCs after SCT.SCT patients undergoing lung transplantation at 20 European centres between 1996 and 2014 were included. Clinical data pre- and post-lung transplantation were reviewed. Propensity score-matched controls were generated from the Eurotransplant and Scandiatransplant registries. Kaplan-Meier survival analysis and Cox proportional hazard regression models evaluating predictors of graft loss were performed.Graft survival at 1, 3 and 5 years of 84%, 72% and 67%, respectively, among the 105 SCT patients proved comparable to controls (p=0.75). Sepsis accounted for 15 out of 37 deaths (41%), with prior mechanical ventilation (HR 6.9, 95% CI 1.0-46.7; p<0.001) the leading risk factor. No SCT-specific risk factors were identified. Recurring malignancy occurred in four patients (4%). Lung transplantation <2 years post-SCT increased all-cause 1-year mortality (HR 7.5, 95% CI 2.3-23.8; p=0.001).Lung transplantation outcomes following SCT were comparable to other end-stage diseases. Lung transplantation should be considered feasible in selected candidates. No SCT-specific factors influencing outcome were identified within this carefully selected patient cohort.

Infectious and Non-infectious Pulmonary Complications of Primary Immunodeficiency Diseases in the USIDNET Registry

Infectious and Non-infectious Pulmonary Complications of Primary Immunodeficiency Diseases in the USIDNET Registry

Effect of reduced-intensity conditioning and the risk of late-onset non-infectious pulmonary complications in pediatric patients.

Late-onset non-infectious pulmonary complications (LONIPCs) contribute to higher morbidity and mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Therefore, we investigated the risk factors of LONIPCs in pediatric patients. Between 2001 and 2011, 74 pediatric patients (range, 7months to 22.7years old; median 6.5years old), including 29 with a primary immunodeficiency, underwent 80 allo-HSCTs at our institution. Sixty-seven patients who survived more than 3months after allo-HSCT were analyzed retrospectively. The median follow-up period was 1 973days (range, 126-5 145days). Nine patients (13.4%) developed LONIPCs between 90 and 3 578days after allo-HSCT. A myeloablative conditioning (MAC) regimen and chronic GVHD were determined as significant risk factors of LONIPCs. None of 18 patients who received the reduced-intensity conditioning (RIC) regimen developed LONIPCs, although there was no difference in overall survival between the MAC and RIC regimen. Notably, two immunodeficient patients who received busulfan-based MAC regimen under 2years old developed LONIPC with no history of chronic GVHD after 5years and 10years from SCT, respectively, suggesting the direct toxicity of busulfan. Our study's findings indicate that the RIC regimen reduces the risk of LONIPCs in pediatric patients.

Clinical and radiological characteristics of patients with late-onset severe restrictive lung defect after hematopoietic stem cell transplantation

BackgroundLate-onset noninfectious pulmonary complications (LONIPCs), which occur more than 3 months after allogeneic hematopoietic stem cell transplantation (HSCT), are major causes of morbidity and mortality after transplantation. Among LONIPCs, we occasionally treat patients with late-onset severe restrictive lung defect after HSCT; however, its clinical features have not been fully elucidated.MethodsA retrospective chart review of a single center on cases of late-onset severe restrictive lung defect after HSCT was performed. Among 453 patients who survived longer than 100 days after allogeneic HSCT with evaluable spirometry data, 12 patients (2.6%) developed late-onset severe restrictive lung defect (i.e., vital capacity percent of predicted less than 60%).ResultsMedian duration from transplantation to diagnosis of late-onset severe restrictive lung defect cases was 44.5 months. Major computed tomography (CT) finding was pleuroparenchymal thickening with volume loss, an evidence of fibrosis, predominantly in upper lobes (n = 7), which was consistent with pleuroparenchymal fibroelastosis. The remaining patients showed unclassifiable interstitial pneumonia pattern (n = 2) and airway-predominant pattern (n = 3). The diffusing capacity for carbon oxide tended to decrease, while the residual volume/total lung capacity ratio tended to increase after HSCT. Of 12 patients, 8 patients died and the median month from diagnosis to death was 33.5 months. Seven patients died of pulmonary or systemic infection, and one patient died due to relapse of the primary disease.ConclusionSevere restrictive lung defect could develop in selected cases in the late-phase after HSCT and could be a unique clinical entity with specific radiographical findings.

Association Between CD4+, Viral Load, and Pulmonary Function in HIV.

The antiretroviral therapy era has shifted the epidemiology of HIV-associated diseases, increasing the recognition of non-infectious pulmonary complications secondary to HIV. We aimed to determine the association between CD4+, viral load, and pulmonary function in individuals with uncontrolled HIV, and determine how changes in these parameters are associated with pulmonary function longitudinally. This is a retrospective observational study of individuals with HIV who underwent pulmonary function testing in an urban medical center between August 1997 and November 2015. Of the 146 participants (mean age 52±10years), 49% were Hispanic, 56% were men, and 44% were current smokers. CD4+ <200cells/μl was associated with significant diffusion impairment compared to CD4+ ≥200cells/μl (DLCO 56 vs. 70%, p=<0.01). VL (viral load) ≥75copies/ml was associated with significant diffusion impairment compared to VL <75copies/ml (DLCO 60 vs. 71%, p=<0.01). No difference in FEV1, FEV1/FVC, or TLC was noted between groups. In univariate analysis, CD4+ and VL correlated with DLCO (r=+0.33; p=<0.01; r=-0.26; p=<0.01) and no correlation was noted with FEV1, FEV1/FVC, or TLC. Current smoking and history of AIDS correlated with DLCO (r=-0.20; p=0.03; r=-0.20; p=0.04). After adjusting for smoking and other confounders, VL ≥75copies/ml correlated with a 11.2 (CI 95% [3.03-19.4], p=<0.01) decrease in DLCO. In Spearman's Rank correlation, there was a negative correlation between change in VL and change in DLCO over time (ρ=-0.47; p=<0.01). The presence of viremia in individuals with HIV is independently associated with impaired DLCO. Suppression of VL may allow for recovery in diffusing capacity over time, though the degree to which this occurs requires further investigation.

16 - Early Post-Transplant Viral Infections and the Incidence of Acute and Chronic Noninfectious Pulmonary Complications Following Hematopoietic Stem Cell Transplantation (HSCT)

16 - Early Post-Transplant Viral Infections and the Incidence of Acute and Chronic Noninfectious Pulmonary Complications Following Hematopoietic Stem Cell Transplantation (HSCT)

Incidence, Risk Factors and Outcome of Late Onset Noninfectious Pulmonary Complications after Allogeneic Hematopoietic Stem Cell Transplantation: A Prospective Cohort Study

Introduction: Late onset noninfectious pulmonary complications (LONIPCs) occurring beyond the third month following allogeneic hematopoietic stem cell transplantation (HSCT) are various and are associated with a poor outcome. Bronchiolitis obliterans (BO) is the most frequent LONIPC. Available epidemiological data are conflicting and exclusively come from retrospective studies.Methods: We conducted a prospective observational cohort study where all consecutive patients who were scheduled to receive an allogeneic HSCT between January, 31, 2006 and December, 31, 2008 at the university-teaching Saint Louis Hospital (Paris, France) were prospectively screened for inclusion in the study. Those allogeneic HSCT recipients surviving at day 100 were included in the cohort. They were followed-up for at least three years after HSCT. Clinical outcomes were the 3-year incidence and mortality of LONIPC, and the identification of early risk factors for LONIPC and specifically BO. This study is registered with ClinicalTrials.gov, number NCT 01219972.Results: 198 patients were included after a median of 101 [IQR: 99-106] days following HSCT, from a total of 243 screened patients. The actual median follow up of the 198 included patients was 72.3 months [IQR: 15.2-88.5]. 68 patients died within the first 36 months resulting in a 3-year overall survival after inclusion of 65.4% (95%CI: 59.1-72.4%). Fifty five episodes of LONIPC were diagnosed in 43 patients. These 55 LONIPC were diagnosed as BO (n=22), interstitial lung disease (n=12), and others. Ten patients had more than one LONIPC during the follow-up. At 36 months after inclusion, the estimated cumulative incidence of LONIPC was 19.8% (95%CI: 14.2-25.3%). The 36 months cumulative incidence of BOS was 10.7%, (95%CI: 6.3-15.1%). 18 patients with a LONIPC died during the follow up with an estimated median survival of 78.5 months (95%CI: 20.0-not reached) after the diagnosis of LONIPC. The occurrence of LONIPC was associated with an increased hazard of death (HR=2.18, 95%CI= 1.14; 4.15; p= 0.0181). Based on a multivariable Cox model, a chest irradiation prior to HSCT, a history of pneumonia within the 100 days post HSCT and a low FEF 25-75 at day 100 were associated with the development of LONIPC. The use of PBSC was predictive for BOS based on a multivariable Cox model both after multiple imputation and on the complete cases whereas both a history of post transplantation pneumonia and bronchial abnormalities on CT scan at day 100 were also identified as predictive factors after multiple imputation and a 10% FEV1 decline from baseline to day 100 was a predictive factor for BOS on the complete cases.Conclusion: our data give clues to identify high-risk patients for developing LONIPC/BO. These patients should be targeted for close monitoring, and so offer earlier treatment of LONIPC or prophylactic treatment to improve the outcome.Funding: The study was supported by an institutional grant from the French Ministry of Health (CRC 04118). DisclosuresPeffault De La Tour:PFIZER: Consultancy, Honoraria, Research Funding; ALEXION: Consultancy, Honoraria, Research Funding; NOVARTIS: Consultancy, Honoraria, Research Funding.

HIV Infection Is Independently Associated with Increased CT Scan Lung Density

Noninfectious pulmonary complications are common among HIV-infected individuals and may be detected early by quantitative computed tomography (CT) scanning. The association of HIV disease markers with CT lung density measurement remains poorly understood. One hundred twenty-five participants free of spirometry-defined lung disease were recruited from a longitudinal cohort study of HIV-infected and HIV-uninfected individuals to undergo standardized CT scan of the chest. Parenchymal density for the entire lung volume was calculated using computerized software. Qualitative assessment of CT scans was conducted by two radiologists masked to HIV status. Linear regression models were developed to determine the independent association of markers of HIV infection on inspiratory scan mean lung density (MLD). HIV-infected participants had a significantly higher MLD (denser lung) compared to HIV-uninfected participants (-815 Hounsfield unit [HU] vs -837 HU; P = 0.002). After adjusting for relevant covariates, HIV infection was independently associated with 19.9 HU higher MLD (95% CI 6.04 to 33.7 HU; P = 0.005). In qualitative assessment, only ground glass attenuation and cysts were noted more commonly among HIV-infected individuals compared to HIV-uninfected individuals (34% vs 17% [P = 0.045] and 27% vs 10% [P = 0.03], respectively). No qualitative radiographic abnormalities attenuated the association between HIV infection and increased MLD. HIV infection is independently associated with increased lung density. Although qualitative CT abnormalities were common in this cohort, only ground glass attenuation and cysts were noted more frequently in HIV-infected participants, suggesting that the increased lung density observed among HIV-infected individuals may be associated with subclinical inflammatory lung changes.

Clinical Predictors of a Diagnosis of Common Variable Immunodeficiency-related Granulomatous-Lymphocytic Interstitial Lung Disease.

Granulomatous-lymphocytic interstitial lung disease (GLILD) has emerged as a major cause of morbidity in patients with common variable immunodeficiency (CVID). While GLILD is among the most serious noninfectious pulmonary complications of CVID, risk factors for this condition have not been reported. To identify clinical, physiologic, and serologic risk factors for GLILD in adults with CVID. Of 345 consecutive adult patients with CVID, we identified 34 in the National Jewish Health research database who had a radiographic-pathologic diagnosis of GLILD evaluated between 2002 and 2014. Each case was age and sex matched to 52 CVID control subjects. We used logistic regression to determine independent predictors of GLILD. A mixed effects model was used to estimate the longitudinal change in percent predicted FVC. The mean time from CVID diagnosis to GLILD detection was 7.8 years. Compared with matched control subjects, cases were more likely to have a history of autoimmune cytopenia, hypersplenism, polyarthritis, lower marginal zone and switched memory B cells, and restrictive lung function. Multivariate analysis revealed that hypersplenism (odds ratio [OR], 24; 95% confidence interval [CI], 4.5-179.1), polyarthritis (OR, 19; 95% CI, 2.3-206.8), and percent predicted FVC (OR, 0.93; 95% CI, 0.87-0.98) were independently associated with the development of GLILD. The rate of change of percent predicted FVC (slope, P = 0.48) did not vary significantly in patients with GLILD over a mean follow-up of 7 years after diagnosis. Hypersplenism and polyarthritis are strong risk factors for GLILD in patients with CVID. Percent predicted FVC remained stable over time in patients with GLILD.

Epidemiology of HIV-Associated Lung Disease in the United States.

The epidemiology of HIV infection and its pulmonary complications in the United States has evolved significantly over nearly 20 years since the advent of combination antiretroviral therapy. While infectious complications are less of a threat to patients whose immune systems have been restored, many HIV-infected persons in the United States remain at high risk for opportunistic infection because they are unaware of their HIV infection, have difficulty maintaining linkage to care, or maintain inadequate viral control. Bacterial pneumonia and Pneumocystis pneumonia remain significantly more prevalent among HIV-infected persons, and together with seasonal influenza are areas where public health efforts to increase antiretroviral therapy, appropriate prophylaxis, and vaccination may decrease burden of disease. Noninfectious pulmonary complications of chronic HIV infection are increasingly recognized in the United States and elsewhere. Chronic obstructive pulmonary disease, asthma, pulmonary hypertension, sleep-disordered breathing, and primary lung cancer may all be more common among persons with HIV; of concern, disease burden in U.S. HIV-infected persons may be underestimated due to lack of diagnostic testing for these conditions. Smoking is among the most prevalent preventable causes of morbidity and mortality affecting persons living with HIV infection, and has particular import to pulmonary disease. As of 2009, 42% of HIV-infected adults in medical care in the United States smoked tobacco (over twice the national rate in the general population). Successful efforts to promote smoking cessation among HIV-infected persons are of critical importance to decrease the burden of chronic pulmonary disease.

Year in review 2015: Interstitial lung disease, pulmonary vascular disease, pulmonary function, sleep and ventilation, cystic fibrosis and paediatric lung disease.

Keywords: interstitial lung disease; lung function; paediatric lung disease; pulmonary vascular disease; sleep

A Pediatric Case of Very Late Onset Non-infectious Pulmonary Complication (LONIPC) after Allogeneic Hematopoietic Stem Cell Transplantation

17-months old infant with Wiskott-Aldrich syndrome was transplanted with genetically two-locus mismatched unrelated cord blood cells under the conditioning regimen of busulfan, cyclophosphamide and anti-thymocyte globulin. GVHD prophylaxis was cyclosporine (CSP) plus short-term methotrexate with prednisolone (1 mg/kg). Acute and chronic GVHD were not observed during the course. About six years later, he suffered from severe cough and dyspnea with no fever, and diagnosed as late onset non-infectious pulmonary complications (LONIPC). We have to be careful for LONIPC after SCT even in the absence of chronic GVHD for younger children because the sign of insidious obstructive pulmonary symptoms is difficult to monitor. To avoid the unexpected LONIPC, introduction of RIC regimen should be considered for younger children, although it has been reported that RIC regimen may increase the risk for GVHD and graft rejection.

Correlation and Agreement of Handheld Spirometry with Laboratory Spirometry in Allogeneic Hematopoietic Cell Transplant Recipients

Early detection of subclinical lung function decline may help identify allogeneic hematopoietic cell transplant (HCT) recipients who are at increased risk for late noninfectious pulmonary complications, including bronchiolitis obliterans syndrome. We evaluated the use of handheld spirometry in this population. Allogeneic HCT recipients enrolled in a single-center observational trial performed weekly spirometry with a handheld spirometer for 1 year after transplantation. Participants performed pulmonary function tests in an outpatient laboratory setting at 3 time points: before transplantation, at day 80 after transplantation, and at 1 year after transplantation. Correlation between the 2 methods was assessed by Pearson and Spearman correlations; agreement was assessed using Bland-Altman plots. A total of 437 subjects had evaluable pulmonary function tests. Correlation for forced expiratory volume in 1 second (FEV1) was r = .954 (P < .0001) at day 80 and r = .931 (P < .0001) at 1 year when the handheld and laboratory tests were performed within 1 day of each other. Correlation for handheld forced expiratory volume in 6 seconds (FEV6) with laboratory forced vital capacity was r = .914 (P < .0001) at day 80 and r = .826 (P < .0001) at 1 year. The bias, or the mean difference (handheld minus laboratory), for FEV1 at day 80 and 1 year was −.13 L (limits of agreement, −.63 to .37) and −.10 L (limits of agreement, −.77 to .56), respectively. FEV6 showed greater bias at day 80 (−.51 L [limits of agreement, −1.44 to .42]) and 1 year (−.40 L [limits of agreement, −1.81 to 1.01]). Handheld spirometry correlated well with laboratory spirometry after allogeneic HCT and may be useful for self-monitoring of patients for early identification of airflow obstruction.