Abnormal Pulmonary Function Tests Research Articles

Relationships of pulmonary function, inflammation, and T-cell activation and senescence in an HIV-infected cohort.

To determine associations between circulating markers of immune activation, immune cell senescence, and inflammation with HIV-associated abnormalities of pulmonary function. HIV infection is an independent risk factor for abnormal pulmonary function. Immune activation, immune senescence, and chronic inflammation are characteristics of chronic HIV infection that have been associated with other HIV-associated comorbidities and may be related to pulmonary disease in this population. Participants from an HIV-infected cohort (n = 147) completed pulmonary function testing (PFT). Markers of T-cell activation and senescence were determined by flow cytometry, and plasma levels of interleukin-6, interleukin-8, and C-reactive protein (CRP) were measured, as was telomere length of peripheral blood mononuclear cells (PBMC). Regression models adjusting for clinical risk factors were constructed to examine relationships between biomarkers and PFT outcomes. Activated CD25(+) T cells and activated/senescent CD69(+)/CD57(+)/CD28(null) CD4(+) T cells, interleukin-6, and CRP were associated with PFT abnormalities. Shortening of PBMC telomere length correlated with airflow obstruction and diffusing impairment. Paradoxically, circulating senescent CD57(+)/CD28(null) CD8(+) T cells were associated with better PFT outcomes. Circulating T cells expressing markers of activation and inflammatory cytokine levels are independently correlated with PFT abnormalities in HIV-infected persons. Overall telomere shortening was also associated with pulmonary dysfunction. The paradoxical association of senescent CD8(+) T cells and better PFT outcomes could suggest an unrecognized beneficial compensatory function of such cells or a redistribution of these cells from the circulation to local compartments. Further studies are needed to differentiate and characterize functional subsets of local pulmonary and circulating T-cell populations in HIV-associated pulmonary dysfunction.

Abnormal Pulmonary Function Testing Before Allogeneic Stem Cell Transplantation Predicts Mortality

Abnormal Pulmonary Function Testing Before Allogeneic Stem Cell Transplantation Predicts Mortality

Effects of blood transfusion on cytokine profile and pulmonary function in patients with thalassemia major.

Thalassemia major (TM) is characterized by abnormal hemoglobin synthesis, which results in decreased oxygen delivery to the tissues, ineffective erythropoiesis and iron overload. The purpose of this study was to find out the predominant type of lung mechanical abnormalities in TM patients, the prevalence of the change in pulmonary diffusing capacity and to search the association of cytokines with pulmonary function tests (PFTs). TM patients (n = 26) who were on regular transfusion program were included in the study. Pretransfusional and posttransfusional PFTs were performed. Before transfusion, blood samples were collected for complete blood count, serum ferritin, zinc, transforming growth factor-β1 (TGF-β1), interleukin (IL)-8 and IL-10 levels. Obstructive lung pattern was the predominant pulmonary sequela. Male gender was the main risk factor for pulmonary function abnormality. Because of very low values, serum IL-10 levels of all patients were undetectable, and serum IL-8 levels could be measured only in six patients. Median serum IL-8 level was higher in patients with abnormal PFT. Pretransfusional single breath diffusion of carbon monoxide (DLCO ) correlated negatively with serum TGF-β1 and ferritin levels. After transfusion, there was a statistically significant decrease in forced expiratory volume in 1 s, forced expiratory flow between 25% and 75% of vital capacity, and airway conductance but significant increase in DLCO . Although they are mostly asymptomatic, TM patients have important PFT abnormalities. Blood transfusion may have an acute deleterious effect on pulmonary functions. The disturbed pulmonary functions were found to correlate with IL-8 and TGF-β levels. Relations of different cytokines with different PFT parameters suggest that the immune system is effective pulmonary dysfunction.

Animal allergen sensitization in veterinarians and laboratory animal workers.

Animals secrete allergens into the environment and exposure to these in the workplace may cause sensitization. To identify the frequency of animal allergen sensitization and symptoms in animal workers. Using skin prick tests (SPT), we assessed sensitization to 15 mammal and bird allergens in animal workers and controls. We also recorded symptoms and pulmonary function tests. There were 100 animal workers and 50 controls included in the study. Thirty-six per cent of animal workers and 10% of controls had positive SPT (P < 0.001, odds ratio [OR] = 5.1, 95% CI 1.7-16.0). The most common sensitizations were to horse (16% in animal workers versus 0% in controls, P < 0.01), canary (16% in animal workers versus 2% in controls, P < 0.05, OR = 9.3, 95% CI 1.2-194), cattle (13% in animal workers versus 0% in controls, P < 0.05), cat (12% in animal workers versus 6% in controls, not significant), rabbit and hamster (10% each in animal workers versus 0% in controls, P < 0.05). Allergy symptoms were reported by 52 animal workers, but only 36 of them had positive SPT. Twelve animal workers had abnormal pulmonary function tests and six had positive SPT. Animal workers are at high risk of occupational sensitization to animal allergens. Exposure should be minimized through control measures and worker education about the risks of exposure and sensitization.

Cardiopulmonary changes in Rheumatoid arthritis

Rheumatoid arthritis should be viewed as a multisystem disease affecting multiple organs. Vigilance for lung and cardiac involvement is necessary among rheumatologists and patients. Despite the absence of effective treatment for advanced respiratory and cardiovascular disease, it is possible that therapeutic intervention at an early stage may be beneficial. Keeping in view the above mentioned facts, we have undertaken this study to see the various cardiac and pulmonary changes associated with rheumatoid arthritis and, their age and sex wise distribution in study population. Objective; To study prevalence and severity of cardiovascular and pulmonary changes in patients of rheumatoid arthritis in accordance to age and sex. Method; All patients fulfilling 1987, revised criteria for diagnosis of rheumatoid arthritis, proposed by American College of Rheumatology were selected without any bias for age, sex, duration, severity of disease. Result; Female to male ratio was 2.6: 1 with hypertension as most common co-morbid disease. Anti-cyclic citrullinated peptide was more specific than rheumatoid factor. 40.5% cases had abnormal pulmonary function test results in the form of restrictive and/or obstructive abnormality. 35.7% had abnormal echocardiography with valvular lesions, pericardial effusion and left ventricular dysfunction in decreasing order. Mitral valve was involved in 87.5% of total valvular involvement. Conclusion; Cardiopulmonary involvement were restrictive pattern of lung involvement along with mitral valve lesions, pericardial effusion and left ventricular dysfunction. Anti-cyclic citrullinated peptide was more specific than rheumatoid factor

AB0922 Pulmonary Involvement in Connective Tissue Diseases - A Retrospective Analysis of A Multidisciplinary Approach

BackgroundThe lung is a frequent target of connective tissue diseases (CTDs) and all components of the respiratory system are at risk. Interstitial lung disease (ILD) is frequently seen in CTDs,...

0136 Respiratory surveillance in Thai automobile workers

ObjectivesTo survey the pulmonary function test in automobile workers.BackgroundThere are some working processes in automobile factory that can affect lung function. Thailand had developed health surveillance in respiratory e.g. predicted...

Pulmonary function abnormalities in childhood cancer survivors treated with bleomycin.

Bleomycin is associated with pulmonary toxic side effects including pneumonitis and pulmonary fibrosis. We evaluated the prevalence of long-term pulmonary function abnormalities in children receiving bleomycin therapy in the context of current chemotherapeutic regimens. A retrospective review of patients who received bleomycin between January 1999 and December 2011 was conducted. Abnormalities in the most recent pulmonary function test (PFT) at least 1 year after diagnosis were analyzed. Two-hundred and seven patients had received bleomycin. The results of PFT performed at least 1 year from diagnosis were available for 80 patients. Median time of follow up was 3.9 years (range 1.1-11.76 years). Median cumulative dose of bleomycin was 65 IU/m(2) (range 10-120). The most common diagnoses were Hodgkin lymphoma and germ cell tumor. At least one pulmonary function abnormality was present in 42 (52.5%) patients. When classified in groups, 22.5% patients had obstructive lung disease, 7.5% had restrictive lung disease, 28.8% had hyperinflation and 14% of patients had non-uniform distribution of ventilation. Non-Hispanic patients (OR 2.81) and children younger than 8 years (OR 4.14) had higher odds of having an abnormal PFT parameter. Very few patients had pulmonary symptoms. More than half the patients who received bleomycin had subclinical pulmonary dysfunction as evidenced by abnormalities in pulmonary function tests, although the incidence of clinical symptoms was low.

Impact of anti-centromere antibodies on pulmonary function test results in patients with systemic sclerosis without established or suspected pulmonary disease.

Pulmonary arterial hypertension (PAH) occurs in approximately 15% of patients with systemic sclerosis (SSc). Annual screening with pulmonary function tests (PFT) is recommended to help identify those patients at risk of PAH. We have noted that patients with SSc who carry anti-centromere autoantibodies (ACA) often have PFT abnormalities, in the absence of clinical evidence of PAH. To evaluate this further, we undertook a retrospective case-control study evaluating PFT results in patients with SSc in whom pulmonary complications have neither been diagnosed nor suspected. Patients were divided according to ACA carriage and groups compared for PFT results. The median forced vital capacity (FVC) was higher in ACA-positive patients (106 vs. 93%, p=0.004). The gas transfer factor (TLco) was significantly lower in the ACA group (62.5 vs. 71%, p=0.013). The resulting FVC:TLco was significantly higher for ACA-positive vs. ACA-negative patients with SSc (1.70 vs. 1.29, p<0.001). Our findings suggest patients carrying ACA, without established or suspected pulmonary complications, have PFT abnormalities consistent with indolent increased pulmonary vascular resistance despite the majority of such patients not subsequently developing PAH. The long-term sequelae of PFT abnormalities in those patients with ACA who do not subsequently develop PAH are unknown.

Pulmonary Involvement in Sjögren Syndrome

Sjögren syndrome (SS) is a chronic autoimmune disease characterized by lymphocytic inflammation of exocrine glands and a variety of extraglandular sites. Lung involvement as defined by symptoms and either pulmonary function testing or radiographic abnormalities occurs in approximately 10 to 20% of patients. Subclinical lung disease is even more frequent and often includes evidence of small airways disease and airway inflammation. In general, patients will have evidence of both airway and interstitial lung disease by radiographs and pathology. Bronchiolitis and bronchiectasis are the most common airway manifestations while the interstitial pathologies associated with SS include nonspecific interstitial pneumonitis, usual interstitial pneumonitis, and lymphocytic interstitial pneumonitis. Patients with SS are also at an increased risk of lymphoma. A protean of other lung abnormalities including amyloidosis, granulomatous lung disease, pseudolymphoma, pulmonary hypertension, and pleural disease have been described.

Correlation of pulmonary function abnormalities with dose volume histograms in children treated with lung irradiation

There is limited data on pulmonary function test (PFT) abnormalities in children treated with modern irradiation techniques. PFT abnormalities have not been correlated with the dose and volume of irradiation. A retrospective chart review of PFTs and clinical outcomes in children who received radiation therapy (RT) at Children's Hospital Los Angeles between 1999 and 2009 was performed. Radiation dose distribution to normal lung tissue was calculated. Forty-nine patients had PFTs available post-RT at a median time of 2.91 years (range, 0.01-8.28) from irradiation. Sixty-seven percent of patients had at least one PFT abnormality on their last available study. The most common abnormality was obstructive lung disease (24%) followed by hyperinflation (20%). Thoracic surgery prior to RT increased the odds of an abnormal FEV1, RV/TLC, and obstructive disease. The sex of the patient, age at the time of irradiation, and time of the PFT after irradiation did not have a significant association with abnormalities. The mean lung dose, maximum lung dose, and prescribed dose of radiation were significantly associated with the development of PFT abnormalities. The odds of developing an abnormal PFT increased with increase in the minimum threshold dose (V(dose)) of radiation, mostly above V(20). PFT abnormalities are common even when modern radiation techniques are used. A significant correlation between radiation parameters and PFT abnormalities was noted.

Long-term pulmonary function after metastasectomy for childhood osteosarcoma: a report from the St Jude lifetime cohort study.

Complete resection of lung metastases improves survival in patients with osteosarcoma. We evaluated the long-term effect of metastasectomy on pulmonary function of patients treated for osteosarcoma during childhood. We reviewed the medical records of patients who had pulmonary function tests (PFTs) after metastasectomy for osteosarcoma. Patient, tumor, and treatment variables were abstracted along with PFTs. The PFTs were recorded as a percentage of predicted value and were classified as abnormal for forced vital capacity (FVC) < 80%, forced expiratory volume in 1 second (FEV1) < 80%, total lung capacity (TLC) < 75%, and single breath diffusion capacity for carbon monoxide corrected for hemoglobin (DLCOcorr) < 75%. Twenty-one patients had PFTs performed during follow-up. Mean age at diagnosis of osteosarcoma was 13.2 ± 4.7 years (SD). Fifteen patients had a single thoracotomy, and 6 patients had ≥2 thoracotomies (range 2 to 6). Eighty lesions were resected. Nine patients had ≤2 lesions resected and 12 patients had >2 lesions (range 3 to 12) resected. Mean time from the last surgical procedure to measurement of PFTs was 20.3 ± 9.0 years (SD). Total lung capacity was abnormal for 28.6%, DLCOcorr for 47.4%, FVC for 40%, and FEV1 for 47.6% of the cohort members. Individual PFTs were abnormal in 13.3% (TLC) to 46.7% (DLCOcorr) of patients who had 1 thoracotomy and in 50.0% (DLCOcorr) to 66.7% (FEV1, TLC) of patients with ≥2 thoracotomies. The number of thoracotomies was associated with abnormal TLC (p = 0.03). Patients who underwent pulmonary metastasectomy for osteosarcoma as children often had abnormal PFTs on long-term follow-up, but the reduction in lung volumes and DLCOcorr was relatively mild. Multiple thoracotomies predicted greater impairment of pulmonary function.

Pulmonary outcomes in patients with Hodgkin lymphoma treated with involved field radiation

Abnormalities in pulmonary function tests (PFT) and clinical symptoms have been reported in up to one third of patients with Hodgkin lymphoma (HL) treated with irradiation. The purpose of this study is to describe the prevalence of pulmonary complications in HL patients treated using contemporary protocols. Eligible patients at Children's Hospital Los Angeles from 1999 to 2009 were identified from the radiation oncology database. Clinical features, radiographic findings, PFT, and radiation details were retrospectively ascertained. The median age at diagnosis of 65 patients with HL was 13.6 years and the median follow-up was 3.7 years. The median prescribed radiation dose was 21 Gy. The prevalence of clinical symptoms was low: chronic cough (3%), dyspnea (9.2%), and supplemental oxygen requirement (1.5%). Radiological interstitial lung changes were observed in 31% of the patients. PFT results following irradiation were available in 38 patients. Forced expiratory volume in 1 second (FEV1) and forced expiratory flow 25-75% (FEF25-75%) were decreased in 13% and 11% of patients respectively. Residual volume (RV) was elevated in 21%. Total Lung capacity (TLC) was decreased in 8%. Age at irradiation (P = 0.004), maximum lung dose (P = 0.03), and volume of lung receiving >25 Gy were associated with development of adverse pulmonary outcomes on univariate analysis. On multivariate analysis, older age was associated with worse outcomes. In survivors of pediatric HL, involved field irradiation was accompanied by a low prevalence of pulmonary symptoms but substantial subclinical dysfunction. Older age at irradiation was associated with worse pulmonary outcomes.

NHANES III equations enhance early detection and mortality prediction of bronchiolitis obliterans syndrome after hematopoietic SCT

Bronchiolitis obliterans syndrome (BOS) is a serious complication of chronic GVHD (cGVHD) following HSCT (hematopoietic SCT). The clinical diagnosis of BOS is based on pulmonary function test (PFT) abnormalities including: FEV1<75% predicted and obstructive FEV1/VC ratio, calculated using reference equations. We sought to determine if the frequency of clinical diagnoses and severity of BOS would be altered by using the recommended NHANES III vs older equations (Morris/Goldman/Bates, MGB) in 166 cGVHD patients, median age 48 (range: 12-67). We found that NHANES III equations significantly increased the prevalence of BOS, with an additional 11% (18/166) meeting diagnostic criteria by revealing low FEV1 (<75%) (P<0.0001), and six additional patients by obstructive ratio (vs MBG). Collectively, this led to an increase of BOS incidence from 17 (29/166) to 29% (41/166). For patients with severe BOS, (FEV1<35%), NHANES III equations correctly predicted death 71.4% vs 50% using MGB. In conclusion, the use of NHANES III equations markedly increases the proportion of cases meeting diagnostic criteria for BOS and improves prediction of survival.

Pulmonary involvement in ankylosing spondylitis assessed by multidetector computed tomography.

SummaryBackgroundAnkylosing spondylitis (AS) may present with extra-articular involvement in the lungs. We aimed to evaluate the abnormal pulmonary multidetector computed tomography findings of patients with AS and compare them with the clinical symptoms, duration of illness, laboratory results and pulmonary function tests (PFT).Material/MethodsWe evaluated the chest multidetector computed tomography (MDCT) findings of 41 patients with ankylosing spondylitis (AS) and compared them with pulmonary function test (PFT) results, demographic characteristics, duration of illness and laboratory findings that we were able to obtain.ResultsThe most common abnormalities were nodules, peribronchial thickening, pleural thickening and bronchiectasis. Abnormalities occurred in 96.87% of patients in the early AS group and 77.8% of patients in the late AS group. Patients with early AS included asymptomatic individuals with normal PFT results and abnormal MDCT findings.ConclusionsThe use of MDCT in AS patients may be beneficial for the evaluation of pulmonary disease, even in asymptomatic patients without any PFT abnormalities and those in the early stages of the disease.

Pulmonary manifestations of inflammatory bowel disease

Extraintestinal manifestations of inflammatory bowel disease (IBD) are a systemic illness that may affect up to half of all patients. Among the extraintestinal manifestations of IBD, those involving the lungs are relatively rare and often overlooked. However, there is a wide array of such manifestations, spanning from airway disease to lung parenchymal disease, thromboembolic disease, pleural disease, enteric-pulmonary fistulas, pulmonary function test abnormalities, and adverse drug reactions. The spectrum of IBD manifestations in the chest is broad, and the manifestations may mimic other diseases. Although infrequent, physicians dealing with IBD must be aware of these conditions, which are sometimes life-threatening, to avoid further health impairment of the patients and to alleviate their symptoms by prompt recognition and treatment. Knowledge of these manifestations in conjunction with pertinent clinical data is essential for establishing the correct diagnosis and treatment. The treatment of IBD-related respiratory disorders depends on the specific pattern of involvement, and in most patients, steroids are required in the initial management. Corticosteroids, both systemic and aerosolized, are the mainstay therapeutic approach, while antibiotics must also be administered in the case of infectious and suppurative processes, whose sequelae sometimes require surgical intervention.

Gender Differences in Pulmonary Function, Respiratory Symptoms, and Macrophage Proteomics among HIV-Infected Smokers.

Background. HIV-infected subjects have an increased incidence of pulmonary emphysema. There are known gender differences in COPD phenotypic expression and diagnosis, but this is not well characterized in lung disease related to HIV. We analyzed a group at risk for the development of COPD (HIV-infected smokers) to determine gender differences in pulmonary symptoms, pulmonary function tests, and HRCT appearances. Methods. This was a cross-sectional, baseline analysis of a prospective study performed between 2006 and 2010. We performed symptomatic, pulmonary function, and computed tomography assessments in 243 HIV-infected smokers. In a subset bronchoalveolar lavage was performed with proteomic analysis of their alveolar macrophages. Results. The majority of the participants were male 213 (87.6%). There was significantly higher percentage of cough and phlegm production in males. There was also a lower FEV1 and a higher RV in males than females. Proteomic analysis revealed 29 proteins with at least a 2-fold higher expression in males and 13 identified proteins that were higher in females. Conclusions. In this group of HIV-infected smokers, airway symptoms and pulmonary function test abnormalities were higher in men than women. These gender differences may be due to differential expression of certain proteins in this group.

Pulmonary involvement in rheumatoid arthritis: multidetector computed tomography findings

Pulmonary involvement in rheumatoid arthritis (RA) is common and encompasses a large spectrum of disease with different treatment options and prognoses. Therefore, assessment of these patients with multidetector computed tomography (MDCT) is vital. To evaluate the MDCT pulmonary findings of patients with RA and to compare these findings with the clinical status. Chest MDCT scans of 85 patients with RA between 2006-2012 were assessed. One patient with a pulmonary infection was excluded from the study. MDCT findings and distribution of the CT findings were examined, and patients were classified according to the predominant CT pattern. The pulmonary function test (PFT) results and categories, demographic characteristics, and clinical status of some of the patients for whom the results were obtained were evaluated, and the CT findings, PFT results, demographic characteristics, and clinical status were compared. The study group consisted of 20 men (mean age, 58.1 years ± 13.1; range, 15-77 years) and 64 women (mean age, 55.3 years ± 11.5; range, 30-84 years). The most frequent findings were nodules (78.6%) and pleural thickening (48.8%). The most common CT patterns were follicular bronchiolitis (FB) in 28 (33.3%) patients and nodular disease (ND) in 12 (14.3%) others. There was no statistically significant difference between the CT findings and PFT results, and no statistically significant difference was noted in the CT findings between symptomatic and asymptomatic patients. In addition, there were some patients who exhibited no symptoms and/or had abnormal PFT results but had abnormal CT findings. Rheumatoid arthritis is associated with a high frequency of CT findings and CT patterns, with nodules and pleural thickening being the most common CT findings and FB and ND being the most common CT patterns. MDCT identification of patients with RA may be helpful in the evaluation of pulmonary disease, even in patients without symptoms and PFT abnormalities.

Pulmonary Function Abnormalities in Non-Splenectomized and Splenectomized Adult Hemoglobin E/β-Thalassemia Patients and Their Correlation With Pulmonary Hypertension

The effect of splenectomy on pulmonary function test (PFT) and pulmonary hypertension (PH) in thalassemia remains unclear. We aimed to investigate PFT and their association with PH in patients with hemoglobin E/β-thalassemia stratified by their splenic status. Thirteen splenectomized patients (SP) and 12 non-splenectomized patients (NSP) were compared regarding to the PFT abnormalities and PH (mean pulmonary artery pressure from right-heart catheterization ≥25 mmHg or estimated systolic pulmonary artery pressure from echocardiography ≥40 mmHg). Eleven (84%) SP and 9 (75%) NSP had restrictive impairment (RI). Of these, more patients having severe RI in SP than in NSP (8 vs. 2, P = 0.035). FVC and PaO2 were lower in SP than in NSP (66 ± 15% vs. 77 ± 12%, P = 0.043, and 79.38 ± 1.6 mmHg vs. 98.83 ± 6.2 mmHg, P &lt; 0.001, respectively). Residual volume was higher in SP than in NSP (78 ± 17% vs. 64 ± 15%, P = 0.036). Seven (54%) SP who developed PH had a longer time interval between splenectomy and the onset of PH than those who did not (17 ± 4.9 years vs. 9.8 ± 6.1 years, P = 0.04). In conclusion, greater severity of extrapulmonary restrictive impairment and hypoxemia were more common in SP. These patients developed PH as a late complication unrelated to hypoxemia and PFT parameters.

Unraveling restrictive chronic lung disease in sickle cell disease [Editorial

A LEADING CAUSE of decreased life expectancy in adults with sickle cell disease (SCD) is acute and chronic lung disease (CLD). CLD historically encompassed both pulmonary f brosis and pulmonary hypertension;1 however, we now understand that these are distinct entities that may not necessarily coexist in SCD patients. While the latter has been the subject of thorough investigations that have determined its high prevalence (approximately 10% by right heart catheterization), strong association with chronic hemolytic anemia, and its relevance as a risk factor for early mortality in SCD,2–5 the former has not been studied comprehensively in the modern era. Pulmonary fibrosis is associated with restrictive lung defects on spirometric evaluation. This is a common finding in adult SCD patients, probably as a result of longstanding chronic inflammation of the small airways from recurrent acute chest syndrome (ACS), infections, vascular infarction and extra-pulmonary restriction.1,6 Longitudinal changes in lung function have also recently been described in children with SCD, with a study reporting an average loss of approximately 3% of forced expiratory volume in one second per year.7,8 Few studies have addressed the pulmonary complications of SCD in sub-Saharan Africa. This is a major area of unmet need, as children with SCD in sub-Saharan Africa are exposed to high rates of pulmonary infectious co-morbidities— predominantly tuberculosis and HIV—expected to exacerbate CLD.9 The article by Cook et al. in this issue of the Journal has focused on determining lung function abnormalities and symptoms of asthma in a cohort of 25 Malawian children with SCD and comparing it to local and international reference ranges.10 The authors reported spirometric abnormalities suggestive of restrictive rather than obstructive defects and the prevalence of wheeze to be comparable to a cohort of children without SCD from urban areas. This is surprising given the high prevalence of obstructive lung disease in areas with high household pollution from burning biomass fuel, such as many urban and rural areas in Malawi.11 Cook et al. hypothesize that in the Malawian SCD population, progression to late stage restrictive lung disease may be occurring earlier and more rapidly with various environmental influences acting as disease modifiers. The authors did not report on history of ACS in the study cohort, but it is possible that an increased number of episodes of ACS might be an important predictor of development of restrictive lung disease at an earlier age. In addition, the small sample size greatly limits the analysis of associated co-morbidities. Despite these limitations, this study provides a useful snapshot of the prevalence of pulmonary function testing abnormalities in an international cohort of pediatric SCD patients. Moreover, it offers the potential to spur further research to develop preventive and therapeutic strategies to alter the pattern of CLD over a larger and varied SCD cohort followed longitudinally. As acknowledged by the authors, a more accurate determination of lung function by provocation testing might be helpful in detecting transient obstructive or even mixed obstructive/restrictive defects. Such studies are required, as asthma has been identified as a significant co-morbidity in SCD and there is growing evidence that a history of ACS in SCD children is a risk factor for reactive airway disease and airway hyper-responsiveness after provocation challenge testing.12–14 Although these are studies of associations and they do not establish causality, asthma exacerbations may precipitate vaso-occlusion and ACS by inducing ventilation-perfusion mismatches.15 In conclusion, this study highlights the importance of restrictive lung impairment in SCD patients, but leaves critical questions unanswered regarding the causes and co-morbidities of interstitial lung disease, as well as the prevalence and role of asthma in SCD outcomes in SCD patients.