Cystic fibrosis: desensitization in delayed hypersensitivity reactions to elexacaftor/tezacaftor/ivacaftor.

Background: Cystic fibrosis transmembrane conductance regulator modulators are the only available treatment for cystic fibrosis. Although elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) is well-tolerated, rash has been reported as very frequent. In severe rashes, ELX/TEZ/IVA withdrawal is necessary, leading to clinical deterioration. The objective of the study is to increment the experience of ELX/TEZ/IVA desensitization. Methods: Adult patients who developed a delayed hypersensitivity rash to ELX/TEZ/IVA between December 2021 and February 2023 and required withdrawal due to ineffective rescue medication were included. Skins test for ELX/TEZ/IVA and IVA were conducted to establish hypersensitivity mechanism. Balijepally ELX/TEZ/IVA desensitization protocol was selected. In cases where desensitization had to be discontinued due to rash, an extended desensitization was proposed. Clinical and health-related quality of life parameters were collected before ELX/TEZ/IVA and after desensitization. Results: 162 patients (81 women, 31.2 [23.8-42.5] years) started ELX/TEZ/IVA, developing rash 12 of them (7.4%, six women). Six patients (five women) required stopping ELX/TEZ/IVA and were selected for desensitization. Skin tests indicated delayed type-IV hypersensitivity in one patient. Two patients presented adequate tolerance to desensitization; while, four patients developed rash. Three of these patients, successfully concluded extended desensitization (one patient declined participation). No significant clinical deterioration or quality of life worsening was observed during desensitization; in fact, there was an improvement in practically all mesured parameters. All five patients who resumed ELX/TEZ/IVA are currently receiving therapy with good tolerance. Conclusion: Desensitization to ELX/TEZ/IVA could be a successful and safe strategy for reintroducing this essential treatment in cases of a delayed hypersensitivity rash.

Severity and outcomes of hospitalised community-acquired pneumonia in COPD patients.

Chronic obstructive pulmonary disease (COPD) is a frequent comorbidity in patients with community-acquired pneumonia (CAP). We investigated the impact of COPD on outcomes of CAP patients. We prospectively studied the clinical presentation of 1,379 patients admitted with CAP during a 4-yr period. A comparative analysis of disease severity and course was performed between 212 patients with COPD, as confirmed by spirometry, and 1,167 non-COPD patients. COPD patients (mean forced expiratory volume in 1 s 47.7 ± 16.3% predicted) were older and more likely to have previously received antibiotics (37.1% versus 28.3%; p<0.01) than those without COPD. They presented with more severe respiratory failure (arterial oxygen tension/inspiratory oxygen fraction 270.4 versus 287.8; p<0.01) and more severe pneumonia (pneumonia severity index 118.3 versus 108.5; p<0.001) compared with non-COPD patients. However, COPD patients had less multilobar infiltration (44 (21%) versus 349 (30%); p<0.01) and fewer pulmonary complications (24 (14%) versus 241 (24%); p<0.01). A total of 89 (6.5%) patients died within 30 days. COPD patients had no significant difference in their 30-day mortality rate compared with non-COPD patients (nine (4.2%) patients versus 81 (7%); p = 0.14). Despite worse clinical presentation, COPD patients had a similar mortality rate compared to non-COPD patients. Previous antibiotic treatment and the decreased incidence of pulmonary complications in COPD may account for these findings.

Factors associated with inflammatory cytokine patterns in community-acquired pneumonia.

Raised systemic levels of interleukin (IL)-6 and IL-10 cytokines have been associated with poorer outcome in community-acquired pneumonia. The aim of our study was to identify potential associated factors with increased levels of IL-6, IL-10, or both cytokines. We performed a prospective study of 685 patients admitted to hospital with community-acquired pneumonia. IL-6 and IL-10 were measured in blood in the first 24 h. 30-day mortality increased from 4.8% to 11.4% (p = 0.003) when both cytokines were higher than the median. Independent associated factors with an excess of IL-6 were neurologic disease, confusion, serum sodium < 130 mEq·L⁻¹, pleural effusion, and bacteraemia. The associated factors for an excess of IL-10 were respiratory rate ≥ 30 breaths·min⁻¹, systolic blood pressure < 90 mmHg and glycaemia ≥ 250 mg·dL⁻¹. The independent associated factors for an excess of both cytokines were confusion, systolic blood pressure < 90 mmHg, pleural effusion and bacteraemia. Protective factors were prior antibiotic treatment and pneumococcal vaccination. Different independent factors are related to an excess of IL-6 and IL-10. Confusion, hypotension, pleural effusion and bacteraemia were associated with the inflammatory profile with the highest mortality rate, whereas anti-pneumococcal vaccination and previous antibiotic treatment appeared to be protective factors.

Influenza pneumonia: a comparison between seasonal influenza virus and the H1N1 pandemic.

We compared clinical presentation, complications and outcome in patients with influenza A (H1N1) and seasonal influenza pneumonia. The group of patients with influenza A (H1N1) pneumonia consisted of 75 patients. 52 patients with pneumonia associated with seasonal influenza were included for comparison. Patients with pneumonia associated with novel H1N1 influenza were younger (mean age 39.7 yrs versus 69.6 yrs) and had fewer chronic comorbidities and less alcoholism. Infiltrates were more extensive and frequently interstitial. Respiratory failure was more frequent (those with an arterial oxygen tension/inspiratory oxygen fraction ratio <200 28% versus 12%, p = 0.042), leading to a higher rate of intensive care unit (ICU) admission and mechanical ventilation (29.3% versus 7.7% (p<0.0030) and 18.7% versus 2% (p<0.0045)). Mortality was twice as high in patients with novel H1N1 (12% versus 5.8%; p = 0.238), although this was not significant, and was attributable to pneumonia in most instances (77.8% versus 0%; p = 0.046). Younger age, fewer comorbidities, more extensive radiographic extension and more severe respiratory compromise, and ICU admissions are key features of the clinical presentation of patients with novel H1N1-associated pneumonia compared with seasonal influenza pneumonia.

Nursing home-acquired pneumonia: a 10 year single-centre experience.

BACKGROUND: Pneumonia among nursing home (NH) residents has increased considerably in recent years, but it remains unclear whether it should be considered as community-acquired pneumonia (CAP) or a new category of infection. METHODS: 150 consecutive cases of NH-acquired pneumonia (NHAP) (from 1 February 1997 to 1 July 2007) were analysed. RESULTS: Patients (median age, 82 years; range, 77-87 years) showed numerous co-morbidities, (neurological, 55%; pulmonary, 38%; cardiac, 35%) and severe disability for daily activities (partial, 32%; total, 31%). Cases of NHAP were mainly classified as mild to moderate according to the CRB-65 score (CRB-65 classes 0-1 and 2, 41% each). In-hospital and 30-day mortality were 8.7% and 20%, respectively. Aetiology was defined in 57 cases (38%). The most common isolates were Streptococcus pneumoniae (58%), Enterobacteriaceae (Gram-negative bacteria (GNB)) (9%), atypical bacteria (7%), respiratory viruses (5%), methicillin-resistant Staphylococcus aureus (MRSA) (5%) and Legionella pneumophila (5%). The most frequent causes of treatment inadequacy were use of beta-lactams alone (25%) and lack of aspiration assessment (15%). Prognostic factors of 1-month mortality were neurological comorbidities (OR 4.5; 95% CI 1.3 to 15.7; p=0.020), septic shock (OR 6.6; 95% CI 1.3 to 34.0; p=0.025), pleural effusion (OR 3.6; 95% CI 1.1 to 11.7; p=0.036) and isolation of GNB or MRSA (OR 16.4; 95% CI 2.1 to 128.9; p=0.008). CONCLUSIONS: The patients show clinical characteristics (eg, age and co-morbidities) comparable with those with hospital-acquired pneumonia. However, microbiological and mortality data of patients with NHAP are more similar to the data of those with CAP. Isolation of GNB or MRSA was associated with increased mortality risk. CAP empirical antibiotic coverage is still indicated in NHAP, although specific risk factors for multidrug-resistant infections should be assessed on an individual basis.

Stability in community-acquired pneumonia: one step forward with markers?

BACKGROUND: Biological markers as an expression of systemic inflammation have been recognised as useful for evaluating the host response in community-acquired pneumonia (CAP). The objective of this study was to evaluate whether the biological markers procalcitonin (PCT) and C-reactive protein (CRP) might reflect stability after 72 h of treatment and the absence of subsequent severe complications. METHODS: A prospective cohort study was performed in 394 hospitalised patients with CAP. Clinical stability was evaluated using modified Halm's criteria: temperature or=90 mm Hg; oxygen saturation >or=90%; or arterial oxygen tension >or=60 mm Hg. PCT and CRP levels were measured on day 1 and after 72 h. Severe complications were defined as mechanical ventilation, shock and/or intensive care unit (ICU) admission, or death after 72 h of treatment. RESULTS: 220 patients achieved clinical stability at 72 h and had significantly lower levels of CRP (4.2 vs 7 mg/dl) and of PCT (0.33 vs 0.48 ng/ml). Regression logistic analyses were performed to calculate several areas under the ROC curve (AUC) to predict severe complications. The AUC for clinical stability was 0.77, 0.84 when CRP was added (p = 0.059) and 0.77 when PCT was added (p = 0.45). When clinical stability was achieved within 72 h and marker levels were below the cut-off points (0.25 ng/ml for PCT and 3 mg/dl for CRP), no severe complications occurred. CONCLUSIONS: Low levels of CRP and PCT at 72 h in addition to clinical criteria might improve the prediction of absence of severe complications.

Short-term effects of three slow expiratory airway clearance techniques in patients with bronchiectasis: a randomised crossover trial.

OBJECTIVE: To compare the efficacy of three slow expiratory airway clearance techniques (ACTs). DESIGN: Randomised crossover trial. SETTING: Tertiary hospital. PARTICIPANTS: Thirty-one outpatients with bronchiectasis and chronic sputum expectoration. INTERVENTIONS: Autogenic drainage (AD), slow expiration with glottis opened in lateral posture (ELTGOL), and temporary positive expiratory pressure (TPEP). MAIN OUTCOMES: Sputum expectoration during each session (primary endpoint) and in the 24-hour period after each session. Leicester Cough Questionnaire (LCQ) score and spirometry results were recorded at the beginning and after each week of treatment. Data were summarised as median difference [95% confidence interval (CI)]. RESULTS: Median (interquartile range) daily expectoration at baseline was 21.1 (15.3 to 35.6)g. During physiotherapy sessions, AD and ELTGOL expectorated more sputum than TPEP [AD vs TPEP 3.1g (95% CI 1.5 to 4.8); ELTGOL vs TPEP 3.6g (95% CI 2.8 to 7.1)], while overall expectoration in the 24-hour period after each session was similar for all techniques (P=0.8). Sputum clearance at 24hours post-intervention was lower than baseline assessment for all techniques [AD vs baseline -10.0g (95% CI -15.0 to -6.8); ELTGOL vs baseline -9.2g (95% CI -14.2 to -7.9); TPEP vs baseline -6.0g (95% CI -12.0 to -6.1)]. The LCQ score increased with all techniques (AD 0.5, 95% CI 0.1 to 0.5; ELTGOL 0.9, 95% CI 0.5 to 2.1; TPEP 0.4, 95% CI 0.1 to 1.2), being similar for all ACTs (P=0.6). No changes in lung function were observed. CONCLUSIONS: Slow expiratory ACTs enhance mucus clearance during treatment sessions, and reduce expectoration for the rest of the day in patients with bronchiectasis. CLINICAL TRIAL REGISTRATION NUMBER: NCT01854788.

Pulmonary complications of pneumococcal community-acquired pneumonia: incidence, predictors, and outcomes.

The aim of this study was to evaluate the clinical characteristics, predictors and outcomes of pneumococcal pneumonia developing pulmonary complications and the distribution of pneumococcal serotypes. It was a prospective study including all adult patients admitted to the Hospital Clinic of Barcelona, Spain (2001-2009) with the diagnosis of pneumococcal pneumonia. Microbiological investigation was systematically performed, including antimicrobial susceptibility and serotype distribution (only invasive strains isolated during 2006-2009). Complicated pneumonia was defined as the presence of one or more pulmonary complications: pleural effusion, empyema, or multilobar infiltrates. We included 626 patients, and 235 (38%) had the following pulmonary complications: pleural effusion, 122 (52%); empyema, 18 (8%); and multilobar infiltration, 151 (64%). Forty-six (20%) patients had more than one complication. Patients with pulmonary complications showed a higher rate of intensive-care unit admission (34% vs. 13%, p <0.001), a higher rate of shock (16% vs. 7%, p <0.001), a longer length of stay (9 days vs. 6 days, p <0.001), and a lower rate of penicillin resistance (14% vs. 25%, p 0.013), but similar mortality (9% vs. 8%). No significant differences were observed in the serotype distribution between complicated and uncomplicated pneumonia. Chronic obstructive pulmonary disease (COPD) (OR 0.38, 95% CI 0.23-0.63; p <0.001) was a protective factor against pulmonary complications, whereas chronic liver disease (OR 3.60, 95% CI 1.71-7.60; p 0.001), admission C-reactive protein level ≥18 mg/dL (OR 2.77, 95% CI 1.91-4.00; p <0.001) and admission creatinine level >1.5 mg/dL (OR 2.01, 95% CI 1.31-3.08; p 0.001) were risk factors for pulmonary complications. Complicated pneumonia was characterized by a more severe clinical presentation, but was not associated with increased mortality. Resistance to antibiotics was lower in complicated cases. No significant differences were observed in the serotype distribution between complicated and uncomplicated pneumonia. In the multivariate analysis, COPD was a protective factor against pulmonary complications.

Community-acquired pneumonia.

Despite the remarkable advances in antibiotic therapies, diagnostic tools, prevention campaigns and intensive care, community-acquired pneumonia (CAP) is still among the primary causes of death worldwide, and there have been no significant changes in mortality in the last decades. The clinical and economic burden of CAP makes it a major public health problem, particularly for children and the elderly. This issue provides a clinical overview of CAP, focusing on epidemiology, economic burden, diagnosis, risk stratification, treatment, clinical management, and prevention. Particular attention is given to some aspects related to the clinical management of CAP, such as the microbial etiology and the available tools to achieve it, the usefulness of new and old biomarkers, and antimicrobial and other non-antibiotic adjunctive therapies. Possible scenarios in which pneumonia does not respond to treatment are also analyzed to improve clinical outcomes of CAP.