Quality of the discussion of asthma on twitter.

IntroductionPatients obtain a large amount of medical information online. Much of this information may not be reliable or of high quality. We investigated what influences the discussion of asthma on Twitter by evaluating the most popular tweets and the quality of the links shared.MethodsWe used Symplur Signals to extract data from Twitter examining characteristics of the top 100 most shared tweets and the 50 most shared links that included the hashtag #asthma. Information on each site was assessed using an Asthma Content score, and validated DISCERN scores and HONCode criteria.ResultsThe top 100 asthma-related tweets were shared 10,169 times and had 16,044 likes. Healthcare organizations posted 49 of the top 100 tweets, non-healthcare individuals posted 20, non-healthcare organizations posted 16 and clinicians posted 14. Of the top 100 tweets, 62 were educational, 11 research-related, 10 political and 15 promotional. The top 50 links were shared 6009 times (median number of shares 92 per link (range 60-710)). Links most commonly (42%) led to educational content while 24% of links led to research articles, 22% to promotional websites, and 12% to political websites. Educational links had higher Asthma Content scores than other links (p < 0.005). Overall, all three scores were low for all types of links. Only 34% of sites met HONCode criteria, and 14% were assessed as high quality by DISCERN score.ConclusionThe top tweets using the hashtag #asthma were commonly educational. The majority of top links on Twitter scored poorly on asthma content, quality, and reliability.

In COPD, prophylactic macrolides, but not tetracyclines or quinolones, reduce exacerbations, with fewer serious adverse events.

SOURCE CITATION: Janjua S, Mathioudakis AG, Fortescue R, et al. Prophylactic antibiotics for adults with chronic obstructive pulmonary disease: a network meta-analysis. Cochrane Database Syst Rev. 2021;1:CD013198. 33448349.

In spontaneous pneumothorax, initial needle aspiration and large- and narrow-bore chest tubes do not differ for success.

SOURCE CITATION: Mummadi SR, de Longpre' J, Hahn PY. Comparative effectiveness of interventions in initial management of spontaneous pneumothorax: a systematic review and a Bayesian network meta-analysis. Ann Emerg Med. 2020;76:88-102. 32115203.

Long-term evaluation of response to omalizumab therapy in real life by a novel multimodular approach: The Real-life Effectiveness of Omalizumab Therapy (REALITY) study.

BACKGROUND: The evidence on long-term real-life response measures to omalizumab therapy in moderate to severe asthma is limited. A universal assessment tool is needed to adequately evaluate response to omalizumab in these patients. OBJECTIVE: To design a multimodular response assessment tool and use it to measure and define response to omalizumab therapy in real-world settings. METHODS: The Real-life Effectiveness of Omalizumab Therapy (REALITY) study is a retrospective, long-term, real-life clinical study that evaluates response in individuals with allergic asthma who received omalizumab between 2004 and 2011. The Standardized Measure to Assess Response to Therapy (SMART) tool was designed to define response (1 year before to after treatment) by 3 modules: (1) physician's subjective assessment of asthma symptoms and control; (2) objective assessment of 6 parameters: improvement by 50% or more for asthma exacerbation, steroid bursts, emergency department visits, and hospitalizations; increase in forced expiratory volume in 1 second of 200 mL or greater; and improved Asthma Control Test score of 3 or higher; -and (3) true responders (patient meeting both module 1 and 2 criteria). Response was assessed and compared for 3 modules at desired time points. RESULTS: A total of 198 patients (mean age, 31.7 years [range, 3-77 years]; 98 [49%] female; mean omalizumab therapy duration, 2.49 years [range, 3 months to 8 years]; mean omalizumab dosage, 473 mg every 4 weeks; median baseline IgE level, 433 IU/mL) were included in this analysis. Overall visit adherence was 78%, although the adherence rate decreased annually by 20%. Response rates assessed by SMART modules were 61.3%, 60.8%, and 41.8% at 16 weeks, 84.8%, 72.2%, and 64.6% at 1 year, 82.4%, 71.2%, and 63.2% at 2 years, and 95.1%, 87.8%, and 85.4% at 5 years for modules 1, 2, and 3, respectively. There were no significant adverse reactions. CONCLUSION: The REALITY study has demonstrated long-term effectiveness of omalizumab therapy in individuals with allergic asthma in real-life settings. The SMART tool is promising as a potential standard assessment tool to measure and define response to asthma therapy. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01776177.

The Immunopathologic Effects of Mycoplasma pneumoniae and Community-acquired Respiratory Distress Syndrome Toxin. A Primate Model.

Mycoplasma pneumoniae infection has been linked to poor asthma outcomes. M. pneumoniae produces an ADP-ribosylating and vacuolating toxin called community-acquired respiratory distress syndrome (CARDS) toxin that has a major role in inflammation and airway dysfunction. The objective was to evaluate the immunopathological effects in primates exposed to M. pneumoniae or CARDS toxin. A total of 13 baboons were exposed to M. pneumoniae or CARDS toxin. At Days 7 and 14, BAL fluid was collected and analyzed for cell count, percent of each type of cell, CARDS toxin by PCR, CARDS toxin by antigen capture, eosinophilic cationic protein, and cytokine profiles. Serum IgM, IgG, and IgE responses to CARDS toxin were measured. All animals had a necropsy for analysis of the histopathological changes on lungs. No animal developed signs of infection. The serological responses to CARDS toxin were variable. At Day 14, four of seven animals exposed to M. pneumoniae and all four animals exposed to CARDS toxin developed histological "asthma-like" changes. T cell intracellular cytokine analysis revealed an increasing ratio of IL-4/IFN-γ over time. Both M. pneumoniae and CARDS toxin exposure resulted in similar histopathological pulmonary changes, suggesting that CARDS toxin plays a major role in the inflammatory response.

Mycoplasma pneumoniae and health outcomes in children with asthma.

BACKGROUND: Acute infections with Mycoplasma pneumoniae (Mp) have been associated with worsening asthma in children. Mp can be present in the respiratory tract for extended periods; it is unknown whether the long-term persistence of Mp in the respiratory tract affects long-term asthma control. OBJECTIVE: To determine the effect of Mp on asthma control. METHODS: We enrolled 31 pediatric subjects 3 to 10 years of age with persistent asthma who completed up to 8 visits over a 24-month period. We detected Mp by antigen capture and polymerase chain reaction. Primary outcome measurements included symptom scores, quality of life, medication scores, oral corticosteroid use, health care usage, school absences, and exhaled breath condensate pH. RESULTS: Low levels of Mp community-acquired respiratory distress syndrome toxin were detected in 20 subjects (64.5%) at enrollment. Subjects with Mp positivity at a given visit had a .579 probability of remaining Mp positive at the subsequent visit, whereas those with Mp negativity had a .348 probability of becoming Mp positive at the following visit. The incidence of Mp overall was higher in the spring and summer months. Overall, we found no significant relation between the detection of Mp and worse outcome measurements at the same visit or at subsequent visits. CONCLUSION: The long-term persistence of Mp in the respiratory tract is common in children with asthma. However, the detection of Mp was not associated significantly with worse asthma symptoms, quality of life, health care usage, school absences, or exhaled breath condensate pH in this pediatric asthma cohort.

Modified release itraconazole amorphous solid dispersion to treat Aspergillus fumigatus: importance of the animal model selection.

Previously, modified release itraconazole in the form of a melt-extruded amorphous solid dispersion based on a pH dependent enteric polymer combined with hydrophilic additives (HME-ITZ), exhibited improved in vitro dissolution properties. These properties agreed with pharmacokinetic results in rats showing high and sustained itraconazole (ITZ) systemic levels. The objective of the present study was to better understand the best choice of rodent model for evaluating the pharmacokinetic and efficacy of this orally administered modified release ITZ dosage form against invasive Aspergillus fumigatus. A mouse model and a guinea pig model were investigated and compared to results previously published. In the mouse model, despite similar levels as previously reported values, plasma and lung levels were variable and fungal burden was not statistically different for placebo controls, HME-ITZ and Sporanox® (ITZ oral solution). This study demonstrated that the mouse model is a poor choice for studying modified release ITZ dosage forms based on pH dependent enteric polymers due to low fluid volume available for dissolution and low intestinal pH. To the contrary, guinea pig was a suitable model to evaluate modified release ITZ dosage forms. Indeed, a significant decrease in lung fungal burden as a result of high and sustained ITZ tissue levels was measured. Sufficiently high intestinal pH and fluids available for dissolution likely facilitated the dissolution process. Despite high ITZ tissue level, the primary therapeutic agent voriconazole exhibited an even more pronounced decrease in fungal burden due to its reported higher clinical efficacy specifically against Aspergillus fumigatus.

Endothelial adhesion molecules and multiple organ failure in patients with severe sepsis.

OBJECTIVE: To determine if serum levels of endothelial adhesion molecules were associated with the development of multiple organ failure (MOF) and in-hospital mortality in adult patients with severe sepsis. DESIGN: This study was a secondary data analysis of a prospective cohort study. SETTING: Patients were admitted to two tertiary intensive care units in San Antonio, TX, between 2007 and 2012. PATIENTS: Patients with severe sepsis at the time of intensive care unit (ICU) admission were enrolled. Inclusion criteria were consistent with previously published criteria for severe sepsis or septic shock in adults. Exclusion criteria included immunosuppressive medications or conditions. INTERVENTIONS: None. MEASUREMENTS: Baseline serum levels of the following endothelial cell adhesion molecules were measured within the first 72h of ICU admission: Intracellular Adhesion Molecule 1 (ICAM-1), Vascular Cell Adhesion Molecule-1 (VCAM-1), and Vascular Endothelial Growth Factor (VEGF). The primary and secondary outcomes were development of MOF (⩾2 organ dysfunction) and in-hospital mortality, respectively. MAIN RESULTS: Forty-eight patients were enrolled in this study, of which 29 (60%) developed MOF. Patients that developed MOF had higher levels of VCAM-1 (p=0.01) and ICAM-1 (p=0.01), but not VEGF (p=0.70) compared with patients without MOF (single organ failure only). The area under the curve (AUC) to predict MOF according to VCAM-1, ICAM-1 and VEGF was 0.71, 0.73, and 0.54, respectively. Only increased VCAM-1 levels were associated with in-hospital mortality (p=0.03). These associations were maintained even after adjusting for APACHE and SOFA scores using logistic regression. CONCLUSIONS: High levels of serum ICAM-1 was associated with the development of MOF. High levels of VCAM-1 was associated with both MOF and in-hospital mortality.

Diagnosis and Management of Sarcoidosis.

Sarcoidosis is a systemic disease of unknown etiology characterized by the presence of noncaseating granulomas in any organ, most commonly the lungs and intrathoracic lymph nodes. A diagnosis of sarcoidosis should be suspected in any young or middle-aged adult presenting with unexplained cough, shortness of breath, or constitutional symptoms, especially among blacks or Scandinavians. Diagnosis relies on three criteria: (1) a compatible clinical and radiologic presentation, (2) pathologic evidence of noncaseating granulomas, and (3) exclusion of other diseases with similar findings, such as infections or malignancy. An early and accurate diagnosis of sarcoidosis remains challenging, because initial presentations may vary, many patients are asymptomatic, and there is no single reliable diagnostic test. Prognosis is variable and depends on epidemiologic factors, mode of onset, initial clinical course, and specific organ involvement. The optimal treatment for sarcoidosis remains unclear, but corticosteroid therapy has been the mainstay of therapy for those with significantly symptomatic or progressive pulmonary disease or serious extrapulmonary disease. Refractory or complex cases may require immunosuppressive therapy. Despite aggressive treatment, some patients may develop life-threatening pulmonary, cardiac, or neurologic complications from severe, progressive disease. End-stage disease may ultimately require lung or heart transplantation for eligible patients.

In vitro and in vivo performance of dry powder inhalation formulations: comparison of particles prepared by thin film freezing and micronization.

Recently, inhaled immunosuppressive agents have attracted increasing attention for maintenance therapy following lung transplantation. The rationale for this delivery approach includes a more targeted and localized delivery to the diseased site with reduced systemic exposure, potentially leading to decreased adverse side effects. In this study, the in vitro and in vivo performance of an amorphous formulation prepared by thin film freezing (TFF) and a crystalline micronized formulation produced by milling was compared for tacrolimus (TAC). Despite the relatively large geometric size, the TFF-processed formulation was capable of achieving deep lung delivery due to its low-density, highly porous, and brittle characteristics. When emitted from a Miat® monodose inhaler, TFF-processed TAC formulations exhibited a fine particle fraction (FPF) of 83.3% and a mass median aerodynamic diameter (MMAD) of 2.26 µm. Single-dose 24-h pharmacokinetic studies in rats demonstrated that the TAC formulation prepared by TFF exhibited higher pulmonary bioavailability with a prolonged retention time in the lung, possibly due to decreased clearance (e.g., macrophage phagocytosis), compared to the micronized TAC formulation. Additionally, TFF formulation generated a lower systemic TAC concentration with smaller variability than the micronized formulation following inhalation, potentially leading to reduced side effects related to the drug in systemic circulation.

Human alveolar lining fluid from the elderly promotes Mycobacterium tuberculosis intracellular growth and translocation into the cytosol of alveolar epithelial cells.

The elderly population is highly susceptible to developing respiratory diseases, including tuberculosis, a devastating disease caused by the airborne pathogen Mycobacterium tuberculosis (M.tb) that kills one person every 18 seconds. Once M.tb reaches the alveolar space, it contacts alveolar lining fluid (ALF), which dictates host-cell interactions. We previously determined that age-associated dysfunction of soluble innate components in human ALF leads to accelerated M.tb growth within human alveolar macrophages. Here we determined the impact of human ALF on M.tb infection of alveolar epithelial type cells (ATs), another critical lung cellular determinant of infection. We observed that elderly ALF (E-ALF)-exposed M.tb had significantly increased intracellular growth with rapid replication in ATs compared to adult ALF (A-ALF)-exposed bacteria, as well as a dampened inflammatory response. A potential mechanism underlying this accelerated growth in ATs was our observation of increased bacterial translocation into the cytosol, a compartment that favors bacterial replication. These findings in the context of our previous studies highlight how the oxidative and dysfunctional status of the elderly lung mucosa determines susceptibility to M.tb infection, including dampening immune responses and favoring bacterial replication within alveolar resident cell populations, including ATs, the most abundant resident cell type within the alveoli.

Efficacy of omalizumab in asthmatic patients with IgE levels above 700 IU/mL: a retrospective study.

BACKGROUND: Omalizumab is approved for patients with poorly controlled asthma with serum IgE levels between 30 and 700 IU/mL and positive test results for perennial allergens. Its efficacy in patients with IgE levels greater than 700 IU/mL is unclear. OBJECTIVE: To evaluate the response of asthmatic patients treated with omalizumab with IgE levels greater than 700 IU/mL. METHODS: Asthmatic patients treated with omalizumab for 6 months or longer with elevated IgE levels were evaluated retrospectively. Emergency department (ED) visits, hospitalizations, change in forced expiratory volume in 1 second, corticosteroid bursts, and Asthma Control Test (ACT) scores were recorded for a period of 6 months before and after treatment. RESULTS: Twenty-six patients with an IgE level greater than 700 IU/mL (group 1) were matched by age, sex, and severity of asthma to patients with an IgE of 30 to 700 IU/mL (group 2). The mean numbers of ED visits before and after treatment were 0.96 vs 0.23 (P = .008) in group 1 and 0.65 vs 015 (P = .02) in group 2. Both group 1 and group 2 had an improvement in asthma control based on the mean ACT score before and after treatment (15.6 vs 18.9 [P = .02] and 15.4 vs 19 [P = .006], respectively). There was also a significant reduction in the frequency of systemic corticosteroid use during the 6 months before and after treatment (2.58 vs 0.96 [P < .001] and 2.62 vs 1.23 [P < .001] systemic steroid treatments, respectively). CONCLUSION: Omalizumab was as effective in reducing ED visits, controlling asthma symptoms, and reducing the need for systemic corticosteroids in patients with IgE levels greater than 700 IU/mL compared with patients with levels of 30 to 700 IU/mL.

Assessing proxy reports: agreement between children with asthma and their caregivers on quality of life.

BACKGROUND: Health-related quality of life (HRQOL) questionnaires are important tools to evaluate health status in children with asthma; however, children with asthma and their caregivers have shown only low to moderate agreement in their responses. OBJECTIVE: To analyze the agreement between children with asthma and their caregivers on HRQOL, specifically in the domains of activity limitation, emotional function, and overall quality of life (QOL). METHODS: We enrolled 79 pediatric patients (ages 5-17 years) with asthma (53 with acute asthma and 26 with refractory asthma) and their caregivers. Children completed the Pediatric Asthma Quality of Life Questionnaire, and caregivers completed the Pediatric Asthma Caregiver's Quality of Life Questionnaire (potential score, 1-7; higher scores indicate better QOL). We used paired t test to examine differences in child and caregiver responses, Pearson correlation to describe patterns of agreement, and multivariate analysis to evaluate the effect of sex, age, and ethnicity on differences in child and caregiver responses. RESULTS: Children with asthma and their caregivers reported similar scores and demonstrated moderate correlation in emotional function and overall QOL. Children reported a significantly better QOL than their caregivers in response to questions about activity limitation (mean score, 4.62 vs 3.49; P < .001). Male children were more likely to differ from their caregivers than females, especially in regard to activity limitation. CONCLUSION: Although caregivers of children with asthma can provide useful proxy information about QOL, their responses cannot be substituted for their children's reports regarding activity limitation. Clinicians and researchers should ask both children and their caregivers about asthma-specific QOL.

Mycoplasma pneumoniae in children with acute and refractory asthma.

BACKGROUND: The presence of Mycoplasma pneumoniae has been associated with worsening asthma in children. Sensitive assays have been developed to detect M pneumoniae-derived community-acquired respiratory distress syndrome (CARDS) toxin. OBJECTIVES: To identify the frequency and persistence of M pneumoniae detection in respiratory secretions of children with and without asthma and to evaluate antibody responses to M pneumoniae and the impact of M pneumoniae on biological markers, asthma control, and quality of life. METHODS: We enrolled 143 pediatric patients (53 patients with acute asthma, 26 patients with refractory asthma, and 64 healthy controls; age range, 5-17 years) during a 20-month period with 2 to 5 follow-up visits. We detected M pneumoniae using CARDS toxin antigen capture and polymerase chain reaction and P1 adhesin polymerase chain reaction. Immune responses to M pneumoniae were determined by IgG and IgM levels directed against CARDS toxin and P1 adhesin. pH was measured in exhaled breath condensates, and asthma control and quality of life were assessed using the Asthma Control Test and Pediatric Asthma Quality of Life Questionnaire. RESULTS: M pneumoniae was detected in 64% of patients with acute asthma, 65% with refractory asthma, and 56% of healthy controls. Children with asthma had lower antibody levels to M pneumoniae compared with healthy controls. Exhaled breath condensate pHs and asthma control and quality of life scores were lower in M pneumoniae-positive patients with asthma. CONCLUSION: The results suggest that M pneumoniae detection is common in children, M pneumoniae detection is associated with worsening asthma, and children with asthma may have poor humoral immune responses to M pneumoniae.

Cystic lung lesions in Sjogren syndrome: analysis of lymphocyte subsets in tissue with clinico-radiologic-pathologic correlation.

Pulmonary complications associated with Sjögren syndrome (SS) have attracted attention in recent years. Sjögren syndrome has been associated with small cyst formation in salivary glands, thymus, and lungs and has been recently brought to the forefront by radiologists due to high-resolution techniques. However, pathologists are less aware of this finding unless clinico-radiologic-pathologic correlation is sought. Formation of large bullae in SS is a rare complication with potential for confusion with other diseases. Here, we present the clinical, radiologic, and pathologic findings in 3 patients with SS associated with multiple pulmonary cystic lesions. All 3 patients had a variable mixed restrictive and obstructive component of the disease. There was good correlation with the pulmonary function tests (PFTs), high-resolution computed tomographic scan, and morphology with regard to the restrictive component. The small cysts appear to correlate with the extent of obstructive changes on the PFTs. However, the large bullae do not, implying noncommunication with the conducting airways. This noncorrelation between the PFTs and extent of bullous disease with predominant involvement of lower lobes in SS enables distinction from bullous emphysema. The mechanism of bulla formation in SS appears to be different from bullous emphysema. A check valve mechanism has been proposed previously in SS, which does not explain cyst formation in the thymus. Alternately, inflammation may play a role with the key suspects being CD4 T-helper cells and perhaps NK cells. This is the first report of a clinico-radiologic-pathologic correlation with analysis of lymphocyte subsets.