Small Airway Disease and Emphysema Are Associated with Future Exacerbations in Smokers with CT-derived Bronchiectasis and COPD: Results from the COPDGene Cohort.

Background Chronic obstructive pulmonary disease (COPD) and bronchiectasis can overlap and share pathologic features, such as small airway disease (SAD). Whether the presence of SAD and emphysema in smokers with CT-derived bronchiectasis is associated with exacerbations is unknown. Purpose To assess whether SAD and emphysema in smokers with CT-derived bronchiectasis are associated with future exacerbations. Materials and Methods SAD and emphysema were quantified using the parametric response map method in former and current heavy smokers with and without bronchiectasis at CT from the COPDGene Study (from July 2009 to July 2018). Exacerbations were prospectively assessed through biannual follow-up. An exacerbation was defined as an increase in or new onset of respiratory symptoms treated with antibiotics and/or corticosteroids. Severe exacerbations were defined as those that required hospitalization. The association of a high burden of SAD (≥15.6%) and high burden of emphysema (≥5%) at CT with exacerbations was assessed with generalized linear mixed models. Results Of 737 participants, 387 (median age, 64 years [interquartile range, 58-71 years]; 223 women) had CT-derived bronchiectasis. During a 9-year follow-up, after adjustment for age, sex, race, body mass index, current smoking status, pack-years, exacerbations before study entry, forced expiratory volume in 1 second, or FEV1, and bronchiectasis severity CT score, high burden of SAD and high burden of emphysema were associated with a higher number of exacerbations per year (relative risk [RR], 1.89 [95% CI: 1.54, 2.33] and 1.37 [95% CI: 1.13, 1.66], respectively; P ≤ .001 for both). Results were comparable among participants with bronchiectasis meeting criteria for COPD (n = 197) (RR, 1.67 [95% CI: 1.23, 2.27] for high burden of SAD and 1.51 [95% CI: 1.20, 1.91] for high burden of emphysema; P ≤ .001 for both). Conclusion In smokers with CT-derived bronchiectasis and chronic obstructive pulmonary disease, structural damage to lung parenchyma and small airways was associated with a higher number of exacerbations per year. Clinical trial registration no. NCT00608764 © RSNA, 2021.

The Lung Mucosa Environment in the Elderly Increases Host Susceptibility to Mycobacterium tuberculosis Infection.

As we age, there is an increased risk for the development of tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) infection. Few studies consider that age-associated changes in the alveolar lining fluid (ALF) may increase susceptibility by altering soluble mediators of innate immunity. We assessed the impact of adult or elderly human ALF during Mtb infection in vitro and in vivo. We identified amplification of pro-oxidative and proinflammatory pathways in elderly ALF and decreased binding capability of surfactant-associated surfactant protein A (SP-A) and surfactant protein D (SP-D) to Mtb. Human macrophages infected with elderly ALF-exposed Mtb had reduced control and fewer phagosome-lysosome fusion events, which was reversed when elderly ALF was replenished with functional SP-A/SP-D. In vivo, exposure to elderly ALF exacerbated Mtb infection in young mice. Our studies demonstrate how the pulmonary environment changes as we age and suggest that Mtb may benefit from declining host defenses in the lung mucosa of the elderly.

Management of asthma COPD overlap.

OBJECTIVE: To review the latest literature on management approaches to patients with asthma chronic obstructive pulmonary disease (COPD) overlap (ACO). DATA SOURCES: Studies and reports were identified from the databases of PubMed/Medline and ClinicalTrials.gov from the US National Institutes of Health and the Cochrane Register of Controlled Trials. STUDY SELECTIONS: Studies on the management of asthma, COPD, and ACO were included in this review. RESULTS: Patients with asthma COPD overlap tend to have greater morbidity than those with asthma or COPD alone, but the information on the best therapeutic approach to this group of patients is still limited. Current treatment recommendations rely on expert opinions, roundtable discussions, and strategy documents, because most clinical studies in asthma and COPD have excluded patients with ACO. Because of the potential risk described in patients with asthma with the use of long-acting 2 agonist monotherapy, initial therapy for patients with ACO is recommended to include a long-acting bronchodilator in conjunction with inhaled corticosteroids. Long-acting muscarinic antagonists are effective in both asthma and COPD and should be considered in ACO as an add-on treatment. If inhaler therapy is not effective, advanced therapies based on phenotyping and identification of treatable traits may be considered. CONCLUSION: Few studies have evaluated prospectively therapies in the ACO population, and future studies need to determine best strategies for the treatment of these patients, focusing on targeting its different phenotypes and its treatable traits.

Asthma COPD overlap: Impact of associated comorbidities.

Asthma and chronic obstructive pulmonary disease (COPD) are common chronic pulmonary conditions worldwide which often coexist. Patients with asthma COPD overlap (ACO) may have worse outcomes than those with either disease alone, for example, more respiratory symptoms and frequent exacerbations, and worse lung function. Additionally, there is a growing interest in factors that affect the disease including comorbid conditions. Indeed, recent studies have demonstrated higher rates of comorbid conditions in the ACO population, but the mechanisms behind these observations remain unclear. The objective of this review is to describe current knowledge and clinical implications of the overlapping features of asthma and COPD, and discuss the prevalence and impact of comorbidities, such as osteoporosis, cardiovascular disease, gastroesophageal reflux disease, and depression, in this subgroup of patients.

Incidence and aetiologies of pulmonary granulomatous inflammation: a decade of experience.

BACKGROUND AND OBJECTIVE: Granulomatous lung disease (GLD) is caused by a wide range of conditions. Often there is a need to correlate pathological findings with clinical, microbiological or radiological data to determine an aetiology. The aim of this study was to determine the different aetiologies of GLD over the past decade. METHODS: Among 2228 consecutive lung specimens from 1999 to 2011, 226 cases (10.1%) were positive for GLD. One hundred ninety patients were retrospectively reviewed and diagnoses were assigned based on availability of histological/clinical/microbiological correlation. RESULTS: A confident, probable and uncertain diagnosis was made in 68.4%, 13.2% and 18.4% patients. The aetiologies comprised infectious, non-infectious and uncertain in 54.7%, 26.8% and 18.4% patients. Mycobacterial infections constituted 27% of all patients, and included atypical, tuberculous and unclassified mycobacteria in order of frequency. Acid-fast bacilli (AFB) were visualized in tissue sections in 29% cases and cultured in 73% cases. Fungal infections comprised 27% of all cases, which included Coccidioides, Cryptococcus, Aspergillus and Histoplasma in order of frequency. Fungi were visualized in tissue sections with Gomori methenamine silver (GMS) stain in 83% patients and cultured in 52% cases. Sarcoidosis was the major non-infectious aetiology, constituting 21% of all patients. Necrosis in granulomas was associated with the presence of infection (P < 0.001). CONCLUSIONS: The aetiology in necrotizing GLD with negative AFB and GMS stains is most likely infectious due to atypical mycobacteria. Coccidioidomycosis was the most common fungal infection. The aetiology in non-necrotizing GLD is most likely non-infectious, probably sarcoidosis.

Risk factors and antibiotic therapy in P. aeruginosa community-acquired pneumonia.

BACKGROUND AND OBJECTIVE: Current guidelines recommend empirical treatment against Pseudomonas aeruginosa in community-acquired pneumonia (CAP) patients with specific risk factors. However, evidence to support these recommendations is limited. We evaluate the risk factors and the impact of antimicrobial therapy in patients hospitalized with CAP due to P. aeruginosa. METHODS: We performed a retrospective population-based study of >150 hospitals. Patients were included if they had a diagnosis of CAP and P. aeruginosa was identified as the causative pathogen. Univariate and multivariate analyses were performed using the presence of risk factors and 30-day mortality as the dependent measures. RESULTS: Seven hundred eighty-one patients with P. aeruginosa pneumonia were identified in a cohort of 62 689 patients with pneumonia (1.1%). Of these, 402 patients (0.6%) were included in the study and 379 (0.5%) were excluded due to health care-associated pneumonia or immunosuppression. In patients with CAP due to P. aeruginosa, 272 (67.8%) had no documented risk factors. These patients had higher rates of dementia and cerebrovascular disease. Empirical antibiotic therapy against P. aeruginosa within the first 48 h of presentation was independently associated with lower 30-day mortality in patients with CAP due to P. aeruginosa (hazard ratio (HR) 0.42, 95% confidence interval (CI): 0.23-0.76) and in patients without risk factors for P. aeruginosa CAP (HR 0.40, 95% CI: 0.21-0.76). CONCLUSIONS: Risk factor recommended by current guidelines only detect one third of the patients admitted with CAP due to P. aeruginosa. Risk factors did not define the whole benefit observed due to empirical therapy covering P. aeruginosa.

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.

Safety of ß-blockers in the acute management of cocaine-associated chest pain.

BACKGROUND: Cocaine is the most commonly abused illegal drug in patients presenting to emergency departments (EDs) because of chest pain and accounts for almost 40% of all drug-related visits. It is not known whether all ß-blockers (BB) and ß1-selective agents or mixed α1/ß-adrenergic antagonists (α1/ß-BB) are safe in the acute management of cocaine-associated chest pain, due to concerns of unopposed α-receptor activity resulting in coronary artery spasm and hypertensive urgency. METHODS: Patients who presented to the EDs of 2 large inner city hospitals because of chest pain and who tested positive for cocaine were identified by retrospective chart review. Demographic characteristics, symptoms, vital signs, electrocardiographic abnormalities, medication use, comorbidities, and troponin values were documented. The presence and type of BB used were studied in relation to peak elevation in troponin T and troponin I. Troponin elevation was defined as a troponin I greater than 0.6 ng/mL and troponin T greater than 0.1 ng/mL if serum creatinine was less than 2 mg/dL. RESULTS: A total of 378 patients were included in the study; of these, 78% (n = 296) were black; 12% (n = 44), white; and 10% (n = 38), of other race. Twelve percent (n = 46) of the patients had typical chest pain, 22% (n = 84) had coronary artery disease, 56% (n = 213) had hypertension, and 21% (n = 79) had diabetes mellitus. The admission electrocardiogram showed changes (ST elevation, ST depression, or T-wave inversion) in 43% (n = 163) of the patients. ß-Blockers were used in 43% (n = 162) of the encounters. Troponin elevation occurred in 11% (n = 42) of patients. There was no difference in the number of patients with troponin rise in the BB and non-BB groups, 22 of 162 vs 20 of 213 (P = .2). There was no difference in mean peak troponin levels in patients with troponin rise who were treated with BB vs no BB, 6.7 vs 5.7 ng/mL (P = .6). There was no difference in mean peak troponin levels in patients with troponin rise who were treated with a ß1-selective agents vs a α1/ß-BB, 7.5 vs 4.1 ng/mL (P = .4). No cases of hypertensive urgency were identified after taking any BB. CONCLUSION: Troponin rise is not uncommon in patients with cocaine-associated chest pain and occurred in 11% of the patients. In patients with cocaine-associated chest pain, BBs did not appear to change the incidence of troponin rise. ß1-Selective BBs did not appear to worsen troponin levels compared with mixed α1/ß-BB.

A marmoset model for Mycobacterium avium complex pulmonary disease.

RATIONALE: Mycobacterium avium complex, is the most common nontuberculous mycobacterial respiratory pathogen in humans. Disease mechanisms are poorly understood due to the absence of a reliable animal model for M. avium complex pulmonary disease. OBJECTIVES: The objectives of this study were to assess the susceptibility, immunologic and histopathologic responses of the common marmoset (Callithrix jacchus) to M. avium complex pulmonary infection. METHODS: 7 adult female marmosets underwent endobronchial inoculation with 108 colony-forming units of M. intracellulare and were monitored for 30 or 60 days. Chest radiograph was assessed at baseline (prior to infection) and at the time of sacrifice (30 days for 3 animals and 60 days for 4 animals), and bronchoalveolar lavage cytokines, histopathology and cultures of the bronchoalveolar lavage, lungs, liver and kidney were assessed at time of sacrifice. Serum cytokines were monitored at baseline and weekly for 30 days for all animals and at 60 days for those alive. Group differences in serum cytokine measurements between those that tested positive versus negative for the M. intracellulare infection were assessed using a series of linear mixed models. MEASUREMENTS AND MAIN RESULTS: Five of seven animals (two at 30 days and three at 60 days of infection) had positive lung cultures for M. intracellulare. Extra-pulmonary cultures were positive in three animals. All animals appeared healthy throughout the study. All five animals with positive lung cultures had radiographic changes consistent with pneumonitis. At 30 days, those with M. intracellulare lung infection showed granulomatous inflammation, while at 60 days there were fewer inflammatory changes but bronchiectasis was noted. The cytokine response in the bronchoalveolar lavage fluid was uniformly greater in the animals with positive M. intracellulare cultures than those without a productive infection, with greater levels at 30-days compared to 60-days. Similarly, serum cytokines were more elevated in the animals that had positive M. intracellulare cultures compared to those without a productive infection, peaking 14-21 days after inoculation. CONCLUSION: Endobronchial instillation of M. intracellulare resulted in pulmonary mycobacterial infection in marmosets with a differential immune response, radiographic and histopathologic abnormalities, and an indolent course consistent with M. avium complex lung infection in humans.

A new tractable method for generating human alveolar macrophage-like cells in vitro to study lung inflammatory processes and diseases.

Alveolar macrophages (AMs) are unique lung resident cells that contact airborne pathogens and environmental particulates. The contribution of human AMs (HAMs) to pulmonary diseases remains poorly understood due to the difficulty in accessing them from human donors and their rapid phenotypic change during in vitro culture. Thus, there remains an unmet need for cost-effective methods for generating and/or differentiating primary cells into a HAM phenotype, particularly important for translational and clinical studies. We developed cell culture conditions that mimic the lung alveolar environment in humans using lung lipids, that is, Infasurf (calfactant, natural bovine surfactant) and lung-associated cytokines (granulocyte macrophage colony-stimulating factor, transforming growth factor-ß, and interleukin 10) that facilitate the conversion of blood-obtained monocytes to an AM-like (AML) phenotype and function in tissue culture. Similar to HAM, AML cells are particularly susceptible to both Mycobacterium tuberculosis and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. This study reveals the importance of alveolar space components in the development and maintenance of HAM phenotype and function and provides a readily accessible model to study HAM in infectious and inflammatory disease processes, as well as therapies and vaccines. IMPORTANCE Millions die annually from respiratory disorders. Lower respiratory track gas-exchanging alveoli maintain a precarious balance between fighting invaders and minimizing tissue damage. Key players herein are resident AMs. However, there are no easily accessible in vitro models of HAMs, presenting a huge scientific challenge. Here, we present a novel model for generating AML cells based on differentiating blood monocytes in a defined lung component cocktail. This model is non-invasive, significantly less costly than performing a bronchoalveolar lavage, yields more AML cells than HAMs per donor, and retains their phenotype in culture. We have applied this model to early studies of M. tuberculosis and SARS-CoV-2. This model will significantly advance respiratory biology research.

Update on Asthma-COPD Overlap (ACO): A Narrative Review.

Although chronic obstructive pulmonary disease (COPD) and asthma are well-characterized diseases, they can coexist in a given patient. The term asthma-COPD overlap (ACO) was introduced to describe patients that have clinical features of both diseases and may represent around 25% of COPD patients and around 20% of asthma patients. Despite the increasing interest in ACO, there are still substantial controversies regarding its definition and its position within clinical guidelines for patients with obstructive lung disease. In general, most definitions indicate that ACO patients must present with non-reversible airflow limitation, significant exposure to smoking or other noxious particles or gases, together with features of asthma. In patients with a primary diagnosis of COPD, the identification of ACO has therapeutic implication because the asthmatic component should be treated with inhaled corticosteroids and some studies suggest that the most severe patients may respond to biological agents indicated for severe asthma. This manuscript aims to summarize the current state-of-the-art of ACO. The definitions, prevalence, and clinical manifestations will be reviewed and some innovative aspects, such as genetics, epigenetics, and biomarkers will be addressed. Lastly, the management and prognosis will be outlined as well as the position of ACO in the COPD and asthma guidelines.

Real-life experience with high-frequency chest wall oscillation vest therapy in adults with non-cystic fibrosis bronchiectasis.

BACKGROUND: High frequency chest wall oscillation (HFCWO) has long been used for airway clearance for patients with cystic fibrosis. Only limited research has evaluated this therapy in adult patients with non-cystic fibrosis bronchiectasis (NCFB). METHODS: Data from 2596 patients from a registry of adult bronchiectasis patients using HFCWO therapy was used to evaluate hospitalization patterns before and after initiation of HFCWO therapy, as well as antibiotic use and self-reported metrics of quality of life. Self-reported outcomes were also reviewed by cross-checking with sampled patient charts and found to be consistent. RESULTS: The number of patients who had at least one respiratory-related hospitalization decreased from 49.1% (192/391) in the year before to 24.0% (94/391) in the year after starting HFCWO therapy (p-value < 0.001). At the same time, the number of patients who required three or more hospitalizations dropped from 14.3% (56/391) to 5.6% (22/391). Patients currently taking oral antibiotics for respiratory conditions decreased from 57.7% upon initiation of therapy to 29.9% within 1 year (p < 0.001). Patients who subjectively rated their "overall respiratory health" as good to excellent increased from 13.6% upon initiation of therapy to 60.5% in 1 year (p < 0.001) and those who rated their "ability to clear your lungs" as good to excellent increased from 13.9% to 76.6% (p < 0.001). CONCLUSION: NCFB patients showed improved self-reported outcomes associated with the initiation of HFCWO therapy as measured by number of hospitalizations, antibiotic use, and the subjective experience of airway clearance. The improvement was observed early on after initiation of therapy and sustained for at least 1 year. The reviews of this paper are available via the supplemental material section.

Positive Pressure Ventilation in Cardiogenic Shock: Review of the Evidence and Practical Advice for Patients With Mechanical Circulatory Support.

Cardiogenic shock (CS) is often complicated by respiratory failure, and more than 80% of patients with CS require respiratory support. Elevated filling pressures from left-ventricular (LV) dysfunction lead to alveolar pulmonary edema, which impairs both oxygenation and ventilation. The implementation of positive pressure ventilation (PPV) improves gas exchange and can improve cardiovascular hemodynamics by reducing preload and afterload of the LV, reducing mitral regurgitation and decreasing myocardial oxygen demand, all of which can help augment cardiac output and improve tissue perfusion. In right ventricular (RV) failure, however, PPV can potentially decrease preload and increase afterload, which can potentially lead to hemodynamic deterioration. Thus, a working understanding of cardiopulmonary interactions during PPV in LV and RV dominant CS states is required to safely treat this complex and high-acuity group of patients with respiratory failure. Herein, we provide a review of the published literature with a comprehensive discussion of the available evidence on the use of PPV in CS. Furthermore, we provide a practical framework for the selection of ventilator settings in patients with and without mechanical circulatory support, induction, and sedation methods, and an algorithm for liberation from PPV in patients with CS.

Benralizumab, an add-on treatment for severe eosinophilic asthma: evaluation of exacerbations, emergency department visits, lung function, and oral corticosteroid use.

There are now multiple monoclonal antibodies targeting different inflammatory pathways of severe asthma. Benralizumab is a recently approved monoclonal antibody indicated for the treatment of severe eosinophilic asthma by targeting a subunit of the IL-5 receptor. Treatment with benralizumab results in significant reductions of blood and tissue eosinophils. Early studies report that this therapy has an adequate safety profile, and this was confirmed in later trials. Phase III studies have shown that benralizumab is effective in reducing the rate of exacerbations and improving asthma symptoms and quality of life in patients with severe eosinophilic asthma. Additionally, treatment with benralizumab has resulted in important reductions in the use of chronic oral corticosteroids. In this review, we evaluate the evidence up to date on the efficacy of benralizumab in severe eosinophilic asthma and explore the implications of this therapy in the ever-growing landscape of therapies for severe asthma.

Reslizumab in the management of poorly controlled asthma: the data so far.

Interleukin-5, an important cytokine in the pathophysiology of asthma, participates in terminal maturation and increases chemotaxis, endothelial adhesion, and activation of eosinophils. Blockade of interleukin-5 activity with monoclonal antibodies have been successful in decreasing eosinophil counts. Reslizumab, a monoclonal antibody that targets interleukin-5, has been studied for the treatment of severe asthma. Several studies have shown that reslizumab can effectively treat severe asthma with an eosinophilic phenotype. Compared to placebo, patients treated with reslizumab had a reduction in the rates of asthma exacerbations and experienced improvement in FEV1 and asthma control questionnaires scores as early as 4 weeks after the therapy was initiated. Reslizumab was not effective in various asthma outcomes in patients without eosinophilia. The adverse events reported were similar in both treatment and placebo groups. Patients should be observed immediately after treatment because anaphylaxis may occur rarely (0.3%) after exposure to reslizumab. Future surveillance studies are still needed to establish the risks of malignancy and safety during pregnancy.

Profile of lebrikizumab and its potential in the treatment of asthma.

Interleukin (IL)-13 has been associated with multiple inflammatory features of asthma. It affects multiple cellular lines in asthma and is a key mediator in airway hyperreactivity and remodeling. Periostin, an extracellular protein, has been used as a surrogate marker of IL-13 activity and has been linked to airway remodeling by inducing subepithelial fibrosis. Lebrikizumab is a humanized monoclonal antibody that targets IL-13. Studies have demonstrated promising results with lebrikizumab therapy in asthma with regard to pulmonary function and exacerbation rates, especially on those patients with surrogate markers of T helper cell type 2-driven inflammation (ie, elevated immunoglobulin E levels, eosinophil counts, periostin levels). Lebrikizumab appears to be a safe therapy, but there are ongoing studies evaluating its efficacy and safety profile. Other therapies that target IL-13 and the receptor of IL-4/IL-13 have been studied, but future studies are needed to determine their role in the treatment of asthma.

Impact of macrolide therapy in patients hospitalized with Pseudomonas aeruginosa community-acquired pneumonia.

BACKGROUND: Several studies have described a clinical benefit of macrolides due to their immunomodulatory properties in various respiratory diseases. We aimed to assess the effect of macrolide therapy on mortality in patients hospitalized for Pseudomonas aeruginosa community-acquired pneumonia (CAP). METHODS: We performed a retrospective population-based study of > 150 hospitals in the US Veterans Health Administration. Patients were included if they had a diagnosis of CAP and P aeruginosa was identified as the causative pathogen. Patients with health-care-associated pneumonia and immunosuppression were excluded. Macrolide therapy was considered when administered within the first 48 h of admission. Univariate and multivariable analyses were performed using 30-day mortality as the dependent measure. RESULTS: We included 402 patients with P aeruginosa CAP, of whom 171 (42.5%) received a macrolide during the first 48 h of admission. These patients were older and white. Macrolide use was not associated with lower 30-day mortality (hazard ratio, 1.14; 95% CI, 0.70-1.83; P = .5). In addition, patients treated with macrolides had no differences in ICU admission, use of mechanical ventilation, use of vasopressors, and length of stay (LOS) compared with patients not treated with macrolides. A subgroup analysis among patients with P aeruginosa CAP in the ICU showed no differences in baseline characteristics and outcomes. CONCLUSIONS: Macrolide therapy in the first 48 h of admission is not associated with decreased 30-day mortality, ICU admission, need for mechanical ventilation, and LOS in hospitalized patients with P aeruginosa CAP. Larger cohort studies should address the benefit of macrolides as immunomodulators in patients with P aeruginosa CAP.

The role of anti-infectives in the treatment of refractory asthma.

Refractory asthma not only has a significant effect on quality of life, but also imposes an economic burden on society. Increasing evidence suggests that there is a pathophysiologic interaction between infection and allergic disease in patients with severe or refractory asthma. Therapeutic trials of macrolides and azoles are being utilized in some patients with refractory asthma who fail to respond to standard therapy. In this article we review the definition of refractory asthma and the potential pathophysiologic interactions between infection and allergic disease. Emerging data suggest that microorganisms and their byproducts may be a therapeutic target in the therapy of patients with severe or refractory asthma.

Enfermedad celíaca: conocimientos actuales: [revisión] / Celiac disease: current knowledge

La enfermedad celíaca es una condición genética y autoinmune causada por la intolerancia de por vida al gluten; una proteina que se encuentra en el trigo, centeno y cebada. en indivíduos genéticamente susceptibles, la ingesta de gluten causa una reacción inmunológica que resulta en la inflamación y atrofia de la mucosa del intestino delgado. anteriormente se creía que la enfermedad celíaca era una enfermedad rara de la niñez. Actualmente se reconoce como una condición común que se puede presentar a cualquier edad. Estudios de prevalencia recientes demuestran que la enfermedad celíaca ocurre aproximadamente en 1 de 300 individuos. aunque es más común en caucásicos, en especial en personas con descendencia europea, la enfermedad celíaca puede afectar a todos los grupos étnicos. A pesar de la alta prevalencia de la enferemedad...