Pseudomonas aeruginosa Lipid A Structural Variants Induce Altered Immune Responses.

Pseudomonas aeruginosa causes chronic lung infection in cystic fibrosis (CF), resulting in structural lung damage and progressive pulmonary decline. P. aeruginosa in the CF lung undergoes numerous changes, adapting to host-specific airway pressures while establishing chronic infection. P. aeruginosa undergoes lipid A structural modification during CF chronic infection, not seen in any other disease state. Lipid A, the membrane anchor of lipopolysaccharide (i.e., endotoxin), comprises the majority of the outer membrane of Gram-negative bacteria and is a potent toll-like receptor (TLR)4 agonist. The structure of P. aeruginosa lipid A is intimately linked with its recognition by TLR4, and subsequent immune response. Prior work has identified P. aeruginosa strains with altered lipid A structures that arise during chronic CF lung infection; however, the impact of P. aeruginosa lipid A structure on airway disease has not been investigated. Here, we show that P. aeruginosa lipid A lacks PagL-mediated deacylation during human airway infection using a direct-from-sample mass spectrometry approach on human bronchoalveolar lavage fluid. This structure triggers increased pro-inflammatory cytokine production by primary human macrophages. Furthermore, alterations in lipid A 2-hydroxylation impact cytokine response in a site-specific manner, independent of CFTR function. Interestingly, there is a CF-specific reduction in IL-8 secretion within the epithelial-cell compartment that only occurs in CF bronchial epithelial cells when infected with CF-adapted P. aeruginosa that lack PagL-mediated lipid A deacylation. Taken together, we show that P. aeruginosa alters its lipid A structure during acute lung infection and that this lipid A structure induces stronger signaling through TLR4.

Nasal airway inflammatory responses and pathogen detection in infants with cystic fibrosis.

BACKGROUND: Detecting airway inflammation non-invasively in infants with cystic fibrosis (CF) is difficult. We hypothesized that markers of inflammation in CF [IL-1ß, IL-6, IL-8, IL-10, IL-17A, neutrophil elastase (NE) and tumor necrosis factor (TNF-α)] could be measured in infants with CF from nasal fluid and would be elevated during viral infections or clinician-defined pulmonary exacerbations (PEx). METHODS: We collected nasal fluid, nasal swabs, and hair samples from 34 infants with CF during monthly clinic visits, sick visits, and hospitalizations. Nasal fluid was isolated and analyzed for cytokines. Respiratory viral detection on nasal swabs was performed using the Luminex NxTAG® Respiratory Pathogen Panel. Hair samples were analyzed for nicotine concentration by reverse-phase high-performance liquid chromatography. We compared nasal cytokine concentrations between the presence and absence of detected respiratory viruses, PEx, and smoke exposure. RESULTS: A total of 246 samples were analyzed. Compared to measurements in the absence of respiratory viruses, mean concentrations of IL-6, IL-8, TNF-α, and NE were significantly increased while IL-17A was significantly decreased in infants positive for respiratory viruses. IL-17A was significantly decreased and NE increased in those with a PEx. IL-8 and NE were significantly increased in infants with enteric pathogen positivity on airway cultures, but not P. aeruginosa or S. aureus. Compared to those with no smoke exposure, there were significantly higher levels of IL-6, IL-10, and NE in infants with detectable levels of nicotine. CONCLUSIONS: Noninvasive collection of nasal fluid may identify inflammation in infants with CF during changing clinical or environmental exposures.

Early Versus Delayed Surgery for Midshaft Clavicle Fractures: A Systematic Review.

Background: Orthopaedic surgeons debate the timing of and necessity for surgical intervention when treating displaced midshaft clavicle fractures (MCFs). This systematic review evaluates the available literature regarding functional outcomes, complication rates, nonunion, and reoperation rates between patients undergoing early versus delayed surgical management of MCFs. Methods: Search strategies were applied in PubMed (Medline), CINAHL (EBSCO), Embase (Elsevier), Sport Discus (EBSCO), and Cochrane Central Register of Controlled Trials (Wiley). Following an initial screening and full-text review, demographic and study outcome data was extracted for comparison between the early fixation and delayed fixation studies. Results: Twenty-one studies were identified for inclusion. This resulted in 1158 patients in the early group and 44 in the delayed. Demographics were similar between groups except for a higher percentage of males in the early group (81.6% vs. 61.4%) and longer time to surgery in the delayed group (4.6 days vs. 14.5 months). Disability of the arm, shoulder, and hand scores (3.6 vs. 13.0) and Constant-Murley scores (94.0 vs. 86.0) were better in the early group. Percentages of initial surgeries resulting in complication (33.8% vs. 63.6%), nonunion (1.2% vs. 11.4%), and nonroutine reoperation (15.8% vs. 34.1%) were higher in the delayed group. Conclusion: Outcomes of nonunion, reoperation, complications, DASH scores, and CM scores favor early surgery over delayed surgery for MCFs. However, given the small cohort of delayed patients who still achieved moderate outcomes, we recommend a shared decision-making style for treatment recommendations regarding individual patients with MCFs. Level of Evidence: II.

Description of a Colocated Comprehensive Care Model for People With Sickle Cell and Comorbid Pulmonary Disease.

Comorbid pulmonary complications in people with sickle cell disease (pwSCD) are associated with high rates of morbidity and mortality, and poor access to care contributes to poor outcomes among this particularly high-risk pwSCD. Our purpose was to describe the population served and the resources required for hematology, pulmonary, nursing, respiratory therapy, social work, genetics, psychology, and school liaison providers to see these patients in an integrated clinic. We abstracted demographic, medication, clinical, and diagnostics data of the pwSCD seen at least once in this clinic from February 1, 2014 to December 10, 2020 from the electronic medical record and identified 145 unique pwSCD. Abnormal lung function and bronchodilator responsiveness were detected in 31% and 42% of participants respectively. Sleep abnormalities were found in over two-thirds of those screened and 65% had ≥1 previous acute chest syndrome episode. This clinic also allowed for direct provider communication and required relatively limited resources to serve a large number of severely affected pwSCD. Given the degree of abnormal respiratory variables detected and the limited resources required to implement this model, studies are warranted to evaluate whether it has the potential to improve outcomes in high-risk populations.

Correlation of defect size with fatty infiltration on MRIs of rotator cuff tendinopathy.

Introduction: Sizable rotator cuff defects with limited muscle atrophy and fat replacement may represent acute traumatic ruptures that are less likely to recur after surgery to close the defect, while closure of defects with poor quality muscle are associated with defect recurrence. These distinct lesions are both referred to as tears. We analyzed the relationship between rotator cuff defect size and muscle quality to determine the relative proportion of sizable defects associated with good muscle and factors associated with muscle deterioration. Material and methods: A cohort of 230 consecutive shoulder MRIs in patients with full-thickness rotator cuff tendon defects, limited acromioclavicular arthrosis (to avoid hindrance of defect measurement), and a duration of symptoms in the radiology report from a large urban center in the United States was evaluated for the measured distance between the supraspinatus tendon edge and the greater tuberosity medial to lateral (coronal plane defect size), anterior to posterior (sagittal plane defect width), and fatty infiltration (Goutallier classification), and atrophy (Warner classification) of the supraspinatus. We sought factors independently associated with fatty infiltration and muscle atrophy in multivariable logistic regression analyses. Results: Forty-nine of 109 shoulders (45%) with a coronal plane defect >20 mm had reasonable muscle quality as defined by Goutallier grade less than 2 and Warner grade less than 2. Both greater fatty infiltration of the supraspinatus muscle and greater supraspinatus muscle atrophy were associated with older age and greater coronal plane defect size. Conclusion: The observation that supraspinatus muscle health deteriorates with age and defect size, but nearly half of the largest defects had good muscle, suggests an important distinction between relatively recent traumatic ruptures and old untreated rupture or gradual attrition that may be obfuscated by referring to all lesions as tears. Level of evidence: Level III; Retrospective diagnostic cohort.

Impact of elexacaftor-tezacaftor-ivacaftor on bacterial colonization and inflammatory responses in cystic fibrosis.

BACKGROUND: Cystic fibrosis (CF) is a multisystem disease with progressive deterioration. Recently, CF transmembrane conductance regulator (CFTR) modulator therapies were introduced that repair underlying protein defects. Objective of this study was to determine the impact of elexacaftor-tezacaftor-ivacaftor (ETI) on clinical parameters and inflammatory responses in people with CF (pwCF). METHODS: Lung function (FEV1 ), body mass index (BMI) and microbiologic data were collected at initiation and 3-month intervals for 1 year. Blood was analyzed at baseline and 6 months for cytokines and immune cell populations via flow cytometry and compared to non-CF controls. RESULTS: Sample size was 48 pwCF, 28 (58.3%) males with a mean age of 28.8 ± 10.7 years. Significant increases in %predicted FEV1 and BMI were observed through 6 months of ETI therapy with no change thereafter. Changes in FEV1 and BMI at 3 months were significantly correlated (r = 57.2, p < 0.01). There were significant reductions in Pseudomonas and Staphylococcus positivity (percent of total samples) in pwCF through 12 months of ETI treatment. Healthy controls (n = 20) had significantly lower levels of circulating neutrophils, interleukin (IL)-6, IL-8, and IL-17A and higher levels of IL-13 compared to pwCF at baseline (n = 48). After 6 months of ETI, pwCF had significant decreases in IL-8, IL-6, and IL-17A levels and normalization of peripheral blood immune cell composition. CONCLUSIONS: In pwCF, ETI significantly improved clinical outcomes, reduced systemic pro-inflammatory cytokines, and restored circulating immune cell composition after 6 months of therapy.

Outcomes before and after providing interdisciplinary hematology and pulmonary care for children with sickle cell disease.

People with sickle cell disease (pwSCD) are at risk of developing lung conditions that complicate their SCD but often face health care access barriers. An interdisciplinary clinic providing pulmonary care for pwSCD was created in 2014 at the Nationwide Children's Hospital (NCH) to address access barriers that may prevent optimized treatment. We hypothesize that pwSCD and pulmonary disease would have fewer hospitalizations for acute chest syndrome (ACS), asthma, and vaso-occlusive episodes in the 2 years after their initial SCD-pulmonary clinic visit compared with the 2 years before. From 2014 to 2020, 119 pwSCD were evaluated in the SCD-pulmonary clinic and followed up at the NCH for at least 2 years before and after this initial visit. Acute care outcomes, pulmonary function, polysomnography, echocardiogram, laboratory, and medication prescribing data were collected and analyzed using the Wilcoxon signed ranked and McNemar tests. The median number of acute care visits for ACS (P < .001) and asthma (P = .006) were significantly lower during the 2 years after pwSCD's initial SCD-pulmonary clinic evaluation compared with the 2 years before. Asthma and allergic rhinitis were more frequently diagnosed and prescriptions for hydroxyurea (P = .005) and inhaled corticosteroids (P = .005) were more common in the post-SCD-pulmonary clinic period. The median number of prescribed systemic corticosteroids was lower in the 2 years after SCD-pulmonary clinic evaluation (P < .0001). Lactate dehydrogenase and white blood cell counts also significantly decreased. Implementing a multidisciplinary SCD-pulmonary clinic is feasible and may allow improved management of pulmonary problems and lead to improvements in the usage of health and acute care.

Cystic fibrosis macrophage function and clinical outcomes after elexacaftor/tezacaftor/ivacaftor.

BACKGROUND: Abnormal macrophage function caused by dysfunctional cystic fibrosis transmembrane conductance regulator (CFTR) is a critical contributor to chronic airway infections and inflammation in people with cystic fibrosis (PWCF). Elexacaftor/tezacaftor/ivacaftor (ETI) is a new CFTR modulator therapy for PWCF. Host-pathogen and clinical responses to CFTR modulators are poorly described. We sought to determine how ETI impacts macrophage CFTR function, resulting effector functions and relationships to clinical outcome changes. METHODS: Clinical information and/or biospecimens were obtained at ETI initiation and 3, 6, 9 and 12 months post-ETI in 56 PWCF and compared with non-CF controls. Peripheral blood monocyte-derived macrophages (MDMs) were isolated and functional assays performed. RESULTS: ETI treatment was associated with increased CF MDM CFTR expression, function and localisation to the plasma membrane. CF MDM phagocytosis, intracellular killing of CF pathogens and efferocytosis of apoptotic neutrophils were partially restored by ETI, but inflammatory cytokine production remained unchanged. Clinical outcomes including increased forced expiratory volume in 1 s (+10%) and body mass index (+1.0 kg·m-2) showed fluctuations over time and were highly individualised. Significant correlations between post-ETI MDM CFTR function and sweat chloride levels were observed. However, MDM CFTR function correlated with clinical outcomes better than sweat chloride. CONCLUSION: ETI is associated with unique changes in innate immune function and clinical outcomes.

Emerging Concepts in Defective Macrophage Phagocytosis in Cystic Fibrosis.

Cystic fibrosis (CF) is caused by mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Chronic inflammation and decline in lung function are major reasons for morbidity in CF. Mutant CFTR expressed in phagocytic cells such as macrophages contributes to persistent infection, inflammation, and lung disease in CF. Macrophages play a central role in innate immunity by eliminating pathogenic microbes by a process called phagocytosis. Phagocytosis is required for tissue homeostasis, balancing inflammation, and crosstalk with the adaptive immune system for antigen presentation. This review focused on (1) current understandings of the signaling underlying phagocytic mechanisms; (2) existing evidence for phagocytic dysregulation in CF; and (3) the emerging role of CFTR modulators in influencing CF phagocytic function. Alterations in CF macrophages from receptor initiation to phagosome formation are linked to disease progression in CF. A deeper understanding of macrophages in the context of CFTR and phagocytosis proteins at each step of phagosome formation might contribute to the new therapeutic development of dysregulated innate immunity in CF. Therefore, the review also indicates future areas of research in the context of CFTR and macrophages.

Long-term pulmonary sequelae in adolescents post-SARS-CoV-2 infection.

RATIONALE: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes long-term pulmonary sequelae in adults, but little is known about pulmonary outcomes in pediatrics. OBJECTIVE(S): The aim of this study was to describe long-term subjective and objective pulmonary abnormalities after SARS-CoV-2 infection in pediatric populations. METHODS: Single-center, retrospective cohort of patients seen in post-coronavirus disease 2019 (COVID-19) pulmonary clinic in 2021. Subjects evaluated had persistent pulmonary symptoms 4 weeks or more after initial infection. Clinical testing included a 6-min walk test (6MWT), chest X-ray, pre- and postbronchodilator spirometry, plethysmography, and diffusion capacity. Patients were followed 2-to-3-months after the initial visit with repeat testing. The primary outcome was the presence of abnormal pulmonary function testing. Secondary measures included variables associated with pulmonary outcomes. RESULTS: Eighty-two adolescents were seen at a median of 3.5 months postinfection, with approximately 80% reporting two or more symptoms at clinic presentation (cough, chest pain, dyspnea at rest, and exertional dyspnea). At follow-up (~6.5 months) exertional dyspnea persisted for most (67%). Spirometry was normal in 77% of patients, but 31% had a positive bronchodilator response. No abnormalities were noted on plethysmography or diffusion capacity. Clinical phenotypes identified included inhaled corticosteroid responsiveness, paradoxical vocal fold motion disorder, deconditioning, and dysautonomia. Multivariable modeling demonstrated that obesity, anxiety, and resting dyspnea were associated with reduced 6MWT, while female sex and resting dyspnea were associated with higher Borg Dyspnea and Fatigues scores. CONCLUSIONS: This is the largest study to date of pediatric patients with long-term pulmonary sequelae post-COVID-19. Identified clinical phenotypes and risk factors warrant further study and treatment.

Sweat metabolomics before and after intravenous antibiotics for pulmonary exacerbation in people with cystic fibrosis.

BACKGROUND: People with cystic fibrosis (PWCF) suffer from acute unpredictable reductions in pulmonary function associated with a pulmonary exacerbation (PEx) that may require hospitalization. PEx symptoms vary between PWCF without universal diagnostic criteria for diagnosis and response to treatment. RESEARCH QUESTION: We characterized sweat metabolomes before and after intravenous (IV) antibiotics in PWCF hospitalized for PEx to determine feasibility and define biological alterations by IV antibiotics for PEx. STUDY DESIGN AND METHODS: PWCF with PEx requiring hospitalization for IV antibiotics were recruited from clinic. Sweat samples were collected using the Macroduct® Sweat Collection System at admission prior to initiation of IV antibiotics and after completion prior to discharge. Samples were analyzed for metabolite changes using ultra-high-performance liquid chromatography/tandem accurate mass spectrometry. RESULTS: Twenty-six of 29 hospitalized PWCF completed the entire study. A total of 326 compounds of known identity were detected in sweat samples. Of detected metabolites, 147 were significantly different between pre-initiation and post-completion of IV antibiotics for PEx (average treatment 14 days). Global sweat metabolomes changed from before and after IV antibiotic treatment. We discovered specific metabolite profiles predictive of PEx status as well as enriched biologic pathways associated with PEx. However, metabolomic changes were similar in PWCF who failed to return to baseline pulmonary function and those who did not. INTERPRETATION: Our findings demonstrate the feasibility of non-invasive sweat metabolomic profiling in PWCF and the potential for sweat metabolomics as a prospective diagnostic and research tool to further advance our understanding of PEx in PWCF.

Factors associated with pain intensity and magnitude of limitations among people with hip and knee arthritis.

BACKGROUND: The pain and limitations associated with osteoarthritis of the hip and knee have a notable variation that does not correspond directly with pathophysiology. The purpose of this study is to assess the influence of location of the arthritis on pain intensity and magnitude of limitations accounting for personal and psychological factors. METHODS: One hundred and fifty four patients with osteoarthritis of the hip (41 patients) or the knee (113 patients) were enrolled in this prospective cross sectional cohort study. Patients answered questionnaires which included demographics, site of arthritis (hip or knee), laterality (unilateral or bilateral), pain intensity, Patient-Reported Outcomes Measurement Information System Physical Function Computer Adaptive Test (PROMIS PF CAT), and psychologic questionnaires including the Tampa Scale of Kinesiophobia (TSK-4), Pain Catastrophizing Scale (PCS-4), Generalized Anxiety Disorder (GAD-2) and Patient-Reported Outcomes Measurement Information System Depression Computer Adaptive Test (PROMIS Dep CAT). Kellgren-Lawrence classification was classified by the treating surgeon. Associations of these factors with pain and function were assessed using bivariate and multivariable regression models. RESULTS: In a multivariable model accounting for potential confounding, magnitude of limitations was independently associated with years of education, work status, time spent exercising, catastrophic thinking (PCS-4), and symptoms of depression. They accounted for 50% of variability in physical function, with the major contributor being catastrophic thinking. The model for pain intensity included time spent exercising and fear of painful movement (TSK-4). Anatomic site and radiographic severity of arthritis were not associated with either physical function or pain in our patient sample. CONCLUSIONS: This study confirms that limitations and pain from osteoarthritis of the hip and knee are more closely related to personal and psychological factors, less effective cognitive coping strategies such as catastrophic thinking and kinesiophobia in particular, than to pathological and anatomical factors such as location and severity of arthritis. Care that incorporates incremental correction of common misconceptions that accompany the nociception from osteoarthritis have the potential to improve function and comfort in people with osteoarthritis. LEVEL OF EVIDENCE: Prognostic Level II.

Oral cysteamine as an adjunct treatment in cystic fibrosis pulmonary exacerbations: An exploratory randomized clinical trial.

BACKGROUND: Emerging data suggests a possible role for cysteamine as an adjunct treatment for pulmonary exacerbations of cystic fibrosis (CF) that continue to be a major clinical challenge. There are no studies investigating the use of cysteamine in pulmonary exacerbations of CF. This exploratory randomized clinical trial was conducted to answer the question: In future pivotal trials of cysteamine as an adjunct treatment in pulmonary exacerbations of CF, which candidate cysteamine dosing regimens should be tested and which are the most appropriate, clinically meaningful outcome measures to employ as endpoints? METHODS AND FINDINGS: Multicentre double-blind randomized clinical trial. Adults experiencing a pulmonary exacerbation of CF being treated with standard care that included aminoglycoside therapy were randomized equally to a concomitant 14-day course of placebo, or one of 5 dosing regimens of cysteamine. Outcomes were recorded on days 0, 7, 14 and 21 and included sputum bacterial load and the patient reported outcome measures (PROMs): Chronic Respiratory Infection Symptom Score (CRISS), the Cystic Fibrosis Questionnaire-Revised (CFQ-R); FEV1, blood leukocyte count, and inflammatory markers. Eighty nine participants in fifteen US and EU centres were randomized, 78 completed the 14-day treatment period. Cysteamine had no significant effect on sputum bacterial load, however technical difficulties limited interpretation. The most consistent findings were for cysteamine 450mg twice daily that had effects additional to that observed with placebo, with improved symptoms, CRISS additional 9.85 points (95% CI 0.02, 19.7) p = 0.05, reduced blood leukocyte count by 2.46x109 /l (95% CI 0.11, 4.80), p = 0.041 and reduced CRP by geometric mean 2.57 nmol/l (95% CI 0.15, 0.99), p = 0.049. CONCLUSION: In this exploratory study cysteamine appeared to be safe and well-tolerated. Future pivotal trials investigating the utility of cysteamine in pulmonary exacerbations of CF need to include the cysteamine 450mg doses and CRISS and blood leukocyte count as outcome measures. CLINICAL TRIAL REGISTRATION: NCT03000348; www.clinicaltrials.gov.

(R)-Roscovitine and CFTR modulators enhance killing of multi-drug resistant Burkholderia cenocepacia by cystic fibrosis macrophages.

Cystic fibrosis (CF) is characterized by chronic bacterial infections and heightened inflammation. Widespread ineffective antibiotic use has led to increased isolation of drug resistant bacterial strains from respiratory samples. (R)-roscovitine (Seliciclib) is a unique drug that has many benefits in CF studies. We sought to determine roscovitine's impact on macrophage function and killing of multi-drug resistant bacteria. Human blood monocytes were isolated from CF (F508del/F508del) and non-CF persons and derived into macrophages (MDMs). MDMs were infected with CF clinical isolates of B. cenocepacia and P. aeruginosa. MDMs were treated with (R)-roscovitine or its main hepatic metabolite (M3). Macrophage responses to infection and subsequent treatment were determined. (R)-roscovitine and M3 significantly increased killing of B. cenocepacia and P. aeruginosa in CF MDMs in a dose-dependent manner. (R)-roscovitine-mediated effects were partially dependent on CFTR and the TRPC6 channel. (R)-roscovitine-mediated killing of B. cenocepacia was enhanced by combination with the CFTR modulator tezacaftor/ivacaftor and/or the alternative CFTR modulator cysteamine. (R)-roscovitine also increased MDM CFTR function compared to tezacaftor/ivacaftor treatment alone. (R)-roscovitine increases CF macrophage-mediated killing of antibiotic-resistant bacteria. (R)-roscovitine also enhances other macrophage functions including CFTR-mediated ion efflux. Effects of (R)-roscovitine are greatest when combined with CFTR modulators or cysteamine, justifying further clinical testing of (R)-roscovitine or optimized derivatives.

Consequences of CRISPR-Cas9-Mediated CFTR Knockout in Human Macrophages.

Macrophage dysfunction is fundamentally related to altered immunity in cystic fibrosis (CF). How genetic deficits in the cystic fibrosis transmembrane conductance regulator (CFTR) lead to these defects remains unknown. Rapid advances in genomic editing such as the clustered regularly interspaced short palindromic repeats associated protein 9 (CRISPR/Cas9) system provide new tools for scientific study. We aimed to create a stable CFTR knockout (KO) in human macrophages in order to study how CFTR regulates macrophage function. Peripheral blood monocytes were isolated from non-CF healthy volunteers and differentiated into monocyte-derived macrophages (MDMs). MDMs were transfected with a CRISPR Cas9 CFTR KO plasmid. CFTR KO efficiency was verified and macrophage halide efflux, phagocytosis, oxidative burst, apoptosis, and cytokine functional assays were performed. CFTR KO in human MDMs was efficient and stable after puromycin selection. CFTR KO was confirmed by CFTR mRNA and protein expression. CFTR function was abolished in CFTR KO MDMs. CFTR KO recapitulated known defects in human CF MDM (CFTR class I/II variants) dysfunction including (1) increased apoptosis, (2) decreased phagocytosis, (3) reduced oxidative burst, and (4) increased bacterial load. Activation of the oxidative burst via nicotinamide adenine dinucleotide phosphate (NADPH) oxidase assembly was diminished in CFTR KO MDMs (decreased phosphorylated p47phox). Cytokine production was unchanged or decreased in response to infection in CFTR KO MDMs. In conclusion, we developed a primary human macrophage CFTR KO system. CFTR KO mimics most pathology observed in macrophages obtained from persons with CF, which suggests that many aspects of CF macrophage dysfunction are CFTR-dependent and not just reflective of the CF inflammatory milieu.

Author Correction: Baseline and Disease-Induced Transcriptional Profiles in Children with Sickle Cell Disease.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.