Impact of Early Referral to Palliative Care in Patients with Interstitial Lung Disease.

Background: Interstitial lung diseases (ILDs) have a major impact on survival and quality of life but only a small percentage of patients are referred for palliative care (PC). Objective: To assess the impact of early PC referral on hospital admissions, emergency department visits, and place of death in the last year of life. Design: This is a single-center retrospective observational study. Setting/Subjects: Subjects were patients with ILDs who attended the respiratory department of Hospital Santa Creu i Sant Pau (Barcelona, Spain) between 2011 and 2019. Results: Of the 51 included patients, 45% received early PC referral. Logistic regression indicated that early PC referral was independently associated with a lower risk of hospital admissions in the last year of life (OR = 0.16; 95% CI 0.03-0.75; p = 0.02) and a lower risk of dying in hospital (OR = 0.11; 95% CI 0.02-0.5; p = 0.009). Conclusion: Early PC referral reduces the need for hospitalization and enables domiciliary death.

Drug related problems in clinical practice: a cross-sectional study on their prevalence, risk factors and associated pharmaceutical interventions.

Drug-related problems (DRP) cause preventable negative health outcomes, especially during hospital admissions. The aim of our study was to examine the prevalence and characteristics of DRP in regular clinical pharmacy, as well as to determine those factors associated with a higher risk of DRP in the hospital setting. We analyzed data from a standardized registry database of regular pharmacy practice (2015- 2016). DRP were classified according to the Pharmaceutical Care Network Europe v6.2 classification. Cross-sectional data were obtained from 1602 adults admitted to medical wards. Crude and adjusted binary logistic regressions were performed to identify associations between potential risk factors and DRP. Overall DRP prevalence was high across medical specialties (45,1%), in a population characterized by advanced age, polypharmacy and multimorbidity. Problems leading to DRP were mainly classified into two domains (effectiveness and adverse reactions), being drug and dose selection the most frequent causes. Interventions were accepted and DRP were totally or partially solved in 74.1% and 4.81% of cases, respectively. In the adjusted model polypharmacy, allergies, BMI > 25 kg/m2 and clearance < 30 mL/min were associated with a higher risk of DRP. The participation of clinical pharmacists into multidisciplinary teams promotes the detection and solution of DRP. Polypharmacy, obesity, renal impairment and allergy are associated with a higher risk of DRP during admission.

Antimicrobial peptides, disease severity and exacerbations in bronchiectasis.

RATIONALE: Recently a frequent exacerbator phenotype has been described in bronchiectasis, but the underlying biological mechanisms are unknown. Antimicrobial peptides (AMPs) are important in host defence against microbes but can be proinflammatory in chronic lung disease. OBJECTIVES: To determine pulmonary and systemic levels of AMP and their relationship with disease severity and future risk of exacerbations in bronchiectasis. METHODS: A total of 135 adults with bronchiectasis were prospectively enrolled at three European centres. Levels of cathelicidin LL-37, lactoferrin, lysozyme and secretory leucocyte protease inhibitor (SLPI) in serum and sputum were determined at baseline by ELISA. Patients were followed up for 12 months. We examined the ability of sputum AMP to predict future exacerbation risk. MEASUREMENTS AND MAIN RESULTS: AMP levels were higher in sputum than in serum, suggesting local AMP release. Patients with more severe disease at baseline had dysregulation of airway AMP. Higher LL-37 and lower SLPI levels were associated with Bronchiectasis Severity Index, lower FEV1 (forced expiratory volume in 1 s) and Pseudomonas aeruginosa infection. Low SLPI levels were also associated with the exacerbation frequency at baseline. During follow-up, higher LL-37 and lower SLPI levels were associated with a shorter time to the next exacerbation, whereas LL-37 alone predicted exacerbation frequency over the next 12 months. CONCLUSIONS: Patients with bronchiectasis showed dysregulated sputum AMP levels, characterised by elevated LL-37 and reduced SLPI levels in the frequent exacerbator phenotype. Elevated LL-37 and reduced SLPI levels are associated with Pseudomonas aeruginosa infection and can predict future risk of exacerbations in bronchiectasis.

Airway Bacterial Load and Inhaled Antibiotic Response in Bronchiectasis.

Rationale: The principal underlying inhaled antibiotic treatment in bronchiectasis is that airway bacterial load drives inflammation, and therefore antibiotic treatment will reduce symptoms. Objectives: To determine the relationship between bacterial load and clinical outcomes, assess the stability of bacterial load over time, and test the hypothesis that response to inhaled antibiotics would be predicted by baseline bacterial load. Methods: We performed three studies. Studies 1 and 2 were prospective studies including adults with bronchiectasis. Study 3 was a post hoc analysis of a randomized trial of inhaled aztreonam. A priori patients were divided into low (<105 cfu/g), moderate (105-106 cfu/g), and high bacterial load (≥107 cfu/g) using quantitative sputum culture. Measurements and Main Results: Bacterial load was a stable trait associated with worse quality of life and more airway inflammation in studies 1, 2, and 3. In study 3, patients with high bacterial load showed an improvement in the primary endpoint (Quality of Life-Bronchiectasis-Respiratory Symptoms Score at Week 4) in favor of aztreonam (mean difference of 9.7 points; 95% confidence interval, 3.4-16.0; P = 0.003). The proportion of patients who achieved an increase above the minimum clinically important difference was higher in the aztreonam group at Week 4 (63% vs. 37%; P = 0.01) and at Week 12 (62% vs. 38%; P = 0.01) only in high bacterial load patients. Conclusions: Improvement of quality of life with inhaled aztreonam was only evident in patients with high bacterial load. Bacterial load may be a useful biomarker of severity of disease and treatment response.

Identification of Pseudomonas aeruginosa and airway bacterial colonization by an electronic nose in bronchiectasis.

RATIONALE: Airway colonization by Potentially Pathogenic Microorganisms (PPM) in bronchiectasis is associated with worse clinical outcomes. The electronic nose is a non-invasive technology capable of distinguishing volatile organic compounds (VOC) in exhaled breath. We aim to explore if an electronic nose can reliably discriminate airway bacterial colonization in patients with bronchiectasis. METHODS: Seventy-three clinically stable bronchiectasis patients were included. PPM presence was determined using sputum culture. Exhaled breath was collected in Tedlar bags and VOC breath-prints were detected by the electronic nose Cyranose 320®. Raw data was reduced to three factors with principal component analysis. Univariate ANOVA followed by post-hoc least significant difference test was performed with these factors. Patients were then classified using linear canonical discriminant analysis. Cross-validation accuracy values were defined by the percentage of correctly classified patients. RESULTS: Forty-one (56%) patients were colonized with PPM. Pseudomonas aeruginosa (n = 27, 66%) and Haemophilus influenzae (n = 7, 17%) were the most common PPM. VOC breath-prints from colonized and non-colonized patients were significantly different (accuracy of 72%, AUROC 0.75, p < 0.001). VOC breath-prints from Pseudomonas aeruginosa colonized patients were significantly different from those of patients colonized with other PPM (accuracy of 89%, AUROC 0.97, p < 0.001) and non-colonized patients (accuracy 73%, AUROC 0.83, p = 0.007). CONCLUSIONS: An electronic nose can accurately identify VOC breath-prints of clinically stable bronchiectasis patients with airway bacterial colonization, especially in those with Pseudomonas aeruginosa.

Anti-Pseudomonas aeruginosa IgG antibodies and chronic airway infection in bronchiectasis.

BACKGROUND: Identification of chronic Pseudomonas aeruginosa (PA) infection is important in the management of bronchiectasis, but requires repeated sputum sampling. We hypothesized that serum anti-PA IgG antibodies could diagnose chronic PA infection at a single visit. METHODS: Clinically stable bronchiectasis patients were studied prospectively. Chronic PA infection was defined as 2 or more positive sputum samples at least 3 months apart and/or failure to clear PA following eradication treatment. Baseline serum anti-PA IgG was determined by a validated ELISA kit. RESULTS: A total of 408 patients were included. Sixty of them (14.7%) had chronic PA infection and had higher anti-PA IgG levels (median 6.2 vs. 1.3 units, p < 0.001). Antibody levels showed direct significant correlations with exacerbation frequency, the bronchiectasis severity index and sputum inflammatory markers. Fifty-seven patients with chronic PA infection had a positive test, giving 95% sensitivity, 74.4% specificity and AUROC of 0.87. During follow-up, 38 patients had a new PA isolation. Eradication at 12 months was achieved in 89.5% of subjects with a negative antibody test and 15.8% of patients with a positive test. CONCLUSIONS: Anti-PA IgG test is highly accurate to detect chronic PA infection in bronchiectasis patients. In addition, it may be a marker of disease severity and treatment response.

Nonantibiotic Adjunctive Therapies for Community-Acquired Pneumonia (Corticosteroids and Beyond): Where Are We with Them?

Community-acquired pneumonia (CAP) is a leading cause of hospitalization, morbidity, and mortality. Despite advances in antibiotic treatments, mortality among patients with CAP is still high. For this reason, interest has been focused on nonantibiotic therapeutic measures directed to the host response rather than the microorganism. The development of an efficacious adjunctive treatment has important implications for reducing mortality in CAP. Some clinical studies performed in the last decade have shown a clinically beneficial effect of corticosteroids, possibly by diminishing local and systemic inflammatory host response. Recent meta-analyses showed faster resolution of symptoms, shorter time to clinically stability, reduction of mechanical ventilation needed, and reduction of mortality in the most severe population, although some methodological limitations must be taken into account. In addition, some studies using statins also suggested improved outcomes due to its anti-inflammatory effect in CAP, although this requires further research. Other adjunctive therapies such as immunoglobulins and stem cells are being explored, but are not yet in the stage of clinical trials. In summary, the use of corticosteroids and other adjuvant treatments are promising in CAP, but more studies are needed to determine their impact on mortality.

Airway Mucin 2 Is Decreased in Patients with Severe Chronic Obstructive Pulmonary Disease with Bacterial Colonization.

RATIONALE: Mucins are essential for airway defense against bacteria. We hypothesized that abnormal secreted airway mucin levels would be associated with bacterial colonization in patients with severe chronic obstructive pulmonary disease (COPD) Objectives: To investigate the relationship between mucin levels and the presence of potentially pathogenic micro-organisms in the airways of stable patients with severe COPD Methods: Clinically stable patients with severe COPD were examined prospectively. All patients underwent a computerized tomography scan, lung function tests, induced sputum collection, and bronchoscopy with bronchoalveolar lavage (BAL) and protected specimen brush. Patients with bronchiectasis were excluded. Secreted mucins (MUC2, MUC5AC, and MUC5B) and inflammatory markers were assessed in BAL and sputum by ELISA. MEASUREMENTS AND MAIN RESULTS: We enrolled 45 patients, with mean age (±SD) of 67 (±8) years and mean FEV1 of 41 (±10) % predicted. A total of 31% (n = 14) of patients had potentially pathogenic micro-organisms in quantitative bacterial cultures of samples obtained by protected specimen brush. Patients with COPD with positive cultures had lower levels of MUC2 both in BAL (P = 0.02) and in sputum (P = 0.01). No differences in MUC5B or MUC5AC levels were observed among the groups. Lower MUC2 levels were correlated with lower FEV1 (r = 0.32, P = 0.04) and higher sputum IL-6 (r = -0.40, P = 0.01). CONCLUSIONS: Airway MUC2 levels are decreased in patients with severe COPD colonized by potentially pathogenic micro-organisms. These findings may indicate one of the mechanisms underlying airway colonization in patients with severe COPD. Clinical trial registered with www.clinicaltrials.gov (NCT01976117).

Secreted mucins and airway bacterial colonization in non-CF bronchiectasis.

BACKGROUND AND OBJECTIVE: Secreted mucins play a key role in antibacterial defence in the airway, but have not previously been characterized in non-cystic fibrosis (CF) bronchiectasis patients. We aim to investigate the relationship between secreted mucins levels and the presence of bacterial colonization due to potentially pathogenic microorganisms (PPM) in the airways of stable bronchiectasis patients. METHODS: Clinically stable bronchiectasis patients were studied prospectively at two centres. Patients with other pulmonary conditions were excluded. Spontaneous sputum was subject to bacterial culture, and secreted mucins (MUC2, MUC5AC and MUC5B) were measured in sputum supernatants by ELISA. RESULTS: A total of 50 patients were included. PPM were identified from sputum samples in 30 (60%), with Pseudomonas aeruginosa (n = 10) and Haemophilus influenzae (n = 10) as the most common PPM. There were no baseline differences among airway colonized and non-colonized patients. Patients with airways colonized by PPM presented higher levels of airway MUC2. No differences in MUC5AC levels were found among groups, whereas MUC5B levels were undetectable. Patients with P. aeruginosa colonization expressed the highest levels of MUC2. High levels of MUC2 and MUC5AC are also correlated with disease severity using the Bronchiectasis Severity Index. CONCLUSIONS: Airway MUC2 levels were higher in bronchiectasis patients colonized with PPM compared with those without airway colonization, especially in patients with P. aeruginosa. These findings suggest that airway-secreted mucins levels may play a role in the pathogenesis of airway infection in non-CF bronchiectasis.