Use of cystic fibrosis inhaled medication before and after elexacaftor/tezacaftor/ivacaftor initiation.

Elexacator/tezacaftor/ivacaftor (ETI) has improved cystic fibrosis (CF) outcomes. A reduction in use of maintenance medication after its initiation has been reported. Seventy-one adult people with CF (PwCF) who are followed in three CF centers and completed one year of treatment with ETI were included in this study. Their use of inhaled dornase-α, colistin, tobramycin, aztreonam and levofloxacin during this period was compared with the corresponding use during one year without ETI, using the Medication Possession Ratio (MPR). MPR was significantly decreased after ETI initiation for dornase-α (67±35% vs 48±40%, p<0.001) and for all four inhaled antibiotics together (62±33% vs 41±37%, p<0.001). The findings of this multi-center, retrospective, study suggest that the initiation of ETI significantly leads to decrease in use of standard inhaled medication in PwCF. The significance of this finding in the course of the disease is yet to be investigated by larger prospective clinical trials.

Monitoring of ECFS quality standards for the clinical management of adults with cystic fibrosis.

BACKGROUND: Although cystic fibrosis (CF) standards of care have been produced and regularly updated, they are not specifically targeting at the adult population. The ECFS Standards of Care Project established an international task force of experts to identify quality standards for adults with CF and assess their adherence. METHODS: This study was composed of two phases. In the first one, a task force of international experts derived from published guidelines and graded ten quality standards for adult CF care using a modified Delphi methodology. In the second phase, an international audit was conducted among adult CF centers to retrospectively validate the quality statements and monitor adherence. RESULTS: The task force identified 10 quality standards specific to the care of adults with CF, mainly based on the 2018 ECFS standards of care. 14 adult CF centers participated in the audit, which showed that most quality standards for the management of CF in adults are met across Europe. Heterogeneity in adherence to standards was found across centers according to geographical setting and centers' characteristics. CONCLUSIONS: The identification of quality standards is a valuable resource for the standardization and monitoring of care delivery across centers taking care of adults with CF.

Incidence of SARS-CoV-2 in people with cystic fibrosis in Europe between February and June 2020.

BACKGROUND: Viral infections can cause significant morbidity in cystic fibrosis (CF). The current Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic could therefore have a serious impact on the health of people with CF (pwCF). METHODS: We used the 38-country European Cystic Fibrosis Society Patient Registry (ECFSPR) to collect case data about pwCF and SARS-CoV-2 infection. RESULTS: Up to 30 June 2020, 16 countries reported 130 SARS-CoV-2 cases in people with CF, yielding an incidence of 2.70/1000 pwCF. Incidence was higher in lung-transplanted patients (n=23) versus non-transplanted patients (n=107) (8.43 versus 2.36 cases/1000). Incidence was higher in pwCF versus the age-matched general population in the age groups <15, 15-24, and 25-49 years (p<0.001), with similar trends for pwCF with and without lung transplant. Compared to the general population, pwCF (regardless of transplantation status) had significantly higher rates of admission to hospital for all age groups with available data, and higher rates of intensive care, although not statistically significant. Most pwCF recovered (96.2%), however 5 died, of whom 3 were lung transplant recipients. The case fatality rate for pwCF (3.85%, 95% CI: 1.26-8.75) was non-significantly lower than that of the general population (7.46%; p=0.133). CONCLUSIONS: SARS-CoV-2 infection can result in severe illness and death for pwCF, even for younger patients and especially for lung transplant recipients. PwCF should continue to shield from infection and should be prioritized for vaccination.

Ophthalmologic manifestations of adult patients with cystic fibrosis.

INTRODUCTION: Cystic fibrosis (CF) is the most common life-shortening recessive genetic disease in Caucasians, affecting primarily the lungs. The objective of our study was to investigate potential ophthalmologic involvement in adult patients with CF. METHODS: Fifty adult patients with cystic fibrosis and 60 age- and sex-matched controls underwent complete ophthalmologic examination including tear-film Break-Up Time (BUT), Macular Thickness, and peripapillary Retinal Nerve Fiber Layer (pRNFL) thickness measurements using Spectral Domain-OCT. RESULTS: CF patients had significantly lower nasal-inferior pRNFL thickness (median 82 IQR 67-102 vs 92.5 IQR 82-107, p = 0.005) and lower percentage of normal tear Break-Up Time (56.0% vs 96.7%, p = 0.001) than healthy controls. All CF patients with BUT <10 s were diagnosed with blepharitis at the time of our assessement. The subgroup of patients homozygous for the most common CF mutation, F508del, had lower nasal-inferior pRNFL thickness (p = 0.014) and lower percentage of normal tear Break-Up Time (p = 0.001) compared to the control group. Additional findings, present in the CF group only, were punctuate retinal hemorrhages (four patients), vessel tortuosity (four patients), snail-track degeneration, and retinal tufts (two patients without refractive error). There were no significant differences in visual acuity, refractive errors, gonioscopic findings, or intraocular pressure between the groups. CONCLUSIONS: Our study is, to the best of our knowledge, the largest ophthalmologic study of patients with cystic fibrosis. We found that CF patients had significantly decreased inferior-quadrant peripapillary retinal nerve fiber layer thickness and decreased tear-film break-up time compared to controls. We highlight the importance of careful regular ophthalmologic assessment and follow-up of these patients.

Microbiology and prognosis assessment of hospitalized patients with aspiration pneumonia: a single-center prospective cohort study.

Aspiration pneumonia has a high incidence in hospitalized patients with community-acquired pneumonia and results in high mortality rates. We aimed to evaluate microbiology and assess prognostic factors of aspiration pneumonia in the setting of a tertiary hospital pulmonology department. Community-acquired (CAAP) and healthcare-associated aspiration pneumonia (HCAAP) cases hospitalized over a period of a year were prospectively followed. Demographic, clinical, biological and radiological data were recorded at admission, while sputum, tracheal aspirates or bronchial washing samples were collected within 48 hours of admission. During hospital stay, therapeutic and supportive measures and resulting complications were recorded. Regression analysis was applied to find statistically significant prognostic factors. The sample consisted of 70 patients (67.1% men); 55.7% of them presented as HCAAP; 94.3% had positive culture of lower respiratory tract specimens with isolation of 115 pathogens, 47 of which were multidrug- or extensively drug-resistant. The most common pathogens were Pseudomonas aeruginosa (37.1%), Klebsiella pneumoniae (27.1%), Staphylococcus aureus (25.7%) and Acinetobacter baumannii (20%). Empiric antimicrobial therapy was combination therapy in 70% and included antipseudomonal and MRSA-targeted antibiotics in 61.4% and 11.4%, respectively. Patients in the HCAAP group had a higher rate of antibiotics usage in the previous trimester, more frequent isolation of resistant strains and were more likely to receive inadequate empiric treatment than those in the CAAP group. In-hospital mortality was 52.2%; no difference between groups was noted. Independent factors of increased mortality were older age (p=0.004), low serum albumin levels (p=0.039), increased radiological involvement (p=0.050) and ineffective initial therapy (p=0.001). We concluded that patients hospitalized for aspiration pneumonia have frequent contact with healthcare services and acquire multidrug-resistant Gram-negative bacteria. Empiric therapy should target these specific microorganisms as its success determines the prognosis.

Evaluation of noninvasive markers for the diagnosis of cystic fibrosis liver disease.

OBJECTIVES: In cystic fibrosis (CF), liver disease (LD) is the third leading cause of mortality. As liver biopsy was considered inconsistent in CFLD diagnosis, a combination of modalities were utilized in the conventional Debray criteria (DC). More recently, noninvasive liver fibrosis biomarkers were applied by Koh et al (New criteria-NC). In the current study, we aimed to evaluate noninvasive biomarkers for the CFLD diagnosis. METHODS: Longitudinal data were collected from a cohort of genetically confirmed CF patients. CFLD was diagnosed by both DC and NC. Apart from transient elastography (TE) > 6.8 kPa, biomarkers incorporated in the NC included AST/ALT-ratio (AAR) ≥ 1, FIB-4 index ≥3.25 and APRI >0.50. RESULTS: 62 patients with CF, [56.5% male, age at enrollment 25 (22-31) years], were prospectively followed-up for 33 (28-36) months. Sixteen (25.8%) and 27 (43.5%) patients met DC and NC, respectively. Twenty-four fulfilling NC had at least one positive biomarker (6 TE, 7 AAR, 6 both TE and AAR, 2 both APRI and AAR and 3 both APRI and TE). Thirteen (48.1%) had diffuse LD/cirrhosis by the NC and all had at least one additional parameter classifying them as CFLD. From the 14 (51.8%) with no-diffuse-LD, 64.3%, 14.3% and 21.4% had 2, 3 and 4 of the necessary modalities incorporated in NC, respectively, confirming their classification as CFLD. TE was 100% specific to rule in CFLD but had a moderate sensitivity. CONCLUSIONS: NC were able to identify 17.7% more CFLD patients compared to DC. The multiple biomarkers incorporated in NC may enhance the ability to detect CFLD.

25-hydroxyvitamin D in malignant pleural disease: a prospective cohort study.

INTRODUCTION: Growing evidence suggests a role of vitamin D in various cancers but the significance of vitamin D in malignant pleural disease remains unexplored. We sought to investigate the concentration and diagnostic role of 25-hydroxyvitamin D (25(OH)D) in malignant pleural effusions. MATERIALS AND METHODS: Prospective study of consecutive treatment-naïve patients with a new diagnosis of pleural effusion. RESULTS: Seventy-eight patients were studied, 45 of whom had malignant pleural effusions. Concentration of 25(OH)D in pleural fluid was significantly higher than serum in both malignant (15.2 ng/mL (9.7, 25.6) versus 10.2 ng/mL (6.4, 17.7), P < .001) and benign (11.4 ng/mL (8.4, 23.6) versus 7.9 (5.9, 16.1), P < .001) pleural disease. Pleural fluid 25(OH)D was almost significantly higher in exudates compared to transudates (P = .050) but it did not differ significantly between malignant and benign effusions (P = .217) and it was not diagnostic for malignant pleural disease (area under the ROC curve .58, 95% CI .45-.71). CONCLUSIONS: In subjects with unselected pleural effusions, 25(OH)D in pleural fluid was not diagnostic for malignant pleural disease. The novel finding of convincingly and consistently higher 25(OH)D in pleural fluid than serum suggests a role for vitamin D in pleural disease and merits further research.

Effects of the 34C>T Variant of the AMPD1 Gene on Immune Function, Multi-Organ Dysfunction, and Mortality in Sepsis Patients.

INTRODUCTION: Adenosine exerts anti-inflammatory and tissue-protective effects during systemic inflammation. While the tissue-protective effects might limit organ damage, its anti-inflammatory properties may induce immunoparalysis and impede bacterial clearance. The common 34C>T loss-of-function variant of AMPD1 (rs17602729) is associated with increased adenosine formation, but effects on immune function and outcome in sepsis patients are unknown. METHODS: The effects of the presence of the 34C>T variant on sepsis susceptibility, immune function, multi-organ dysfunction, and mortality in septic patients were studied. Patients suffering from community acquired pneumonia (CAP, initial cohort n = 285; replication cohort n = 212) and ventilator-associated pneumonia (VAP, n = 117; n = 33) and control patients without infection (n = 101) were enrolled. Genetic distributions of the AMPD1 SNP were CC 76%, CT 22%, and TT 2% in the initial cohort and CC 80%, CT 18%, and TT 2% in the replication cohort. RESULTS: The occurrence of septic CAP, but not septic VAP, was increased for the CT versus CC genotype (OR (95% CI) 2.0 (1.1-3.7); P = 0.02) in the initial cohort. The increased risk for the CT versus CC genotype was also observed in the replication cohort but did not reach statistical significance there (P = 0.38), resulting in an OR of the total group of 1.7 (95% CI 1.0-3.1), P = 0.07. In septic patients carrying the CT genotype, the ex vivo production of TNF-α by LPS-stimulated monocytes was attenuated (P = 0.005), indicative of a more pronounced immunoparalytic state in these patients. CONCLUSIONS: Presence of the AMPD1 34C>T variant is associated with higher infection susceptibility to CAP, but not to VAP. More pronounced immunoparalysis in these patients mediated by the anti-inflammatory effects of adenosine may account for this observation.

A prospective study on bacterial and atypical etiology of acute exacerbation in chronic obstructive pulmonary disease.

AIM: The bacterial and atypical etiology of acute exacerbations of chronic obstructive pulmonary disease was investigated and the diagnostic techniques used were compared among 92 hospitalized patients. MATERIALS & METHODS: Sputum specimens were investigated using culture and PCR, serological status evaluation was performed and the inflammatory profile was associated with the microbiological results. RESULTS & CONCLUSION: The majority of the patients (65.2%) had very severe airway obstruction. The most common bacteria were Haemophilus influenzae and Pseudomonas aeruginosa (23.9 and 14.1%, respectively). Acinetobacter baumannii- and P. aeruginosa-positive cultures were associated with prolonged hospitalization and severe airway obstruction (p = 0.03 and 0.031, respectively). Chlamydia pneumoniae or Mycoplasma pneumoniae infection was diagnosed in four and two patients, respectively. Discrepant results were detected between PCR and serology, especially regarding C. pneumoniae.

Prediction of hospitalization stay in COPD exacerbations: the AECOPD-F score.

BACKGROUND: Hospital admissions for COPD exacerbations account for 70% of total costs of COPD treatment, and the duration of hospital stay is directly related to this cost. The aim of this study was to investigate possible associations of demographic, clinical, laboratory, and functional parameters with stay of subjects admitted for COPD exacerbations and to provide a score for the prediction of the need for prolonged hospitalization. METHODS: We included 164 consecutive subjects admitted to 2 respiratory medicine departments of 2 tertiary hospitals for a COPD exacerbation, and we evaluated laboratory, clinical, and functional parameters possibly related to the duration of hospital stay. RESULTS: Seven parameters evaluated on subject admission (Antonisen type of exacerbation, number of Exacerbations in the previous year, Charlson index of comorbidities, Oxygenation, Partial pressure of P(aCO2) in arterial blood gases, Dyspnea according to the Borg dyspnea scale, and history of chronic respiratory Failure) were able to predict stay and were included in a simple score named AECOPD-F. The area under the curve of the score for the prediction of prolonged hospital stay is 0.960, and a cutoff point ≥ 3 predicts prolonged stay with a sensitivity of 84.5% and a specificity of 92.5% (95% CI 0.917-0.984). The AECOPD-F score was validated in a second group of 88 subjects admitted to the hospital for a COPD exacerbation. In the validation group, subjects with a score ≥ 3 required prolonged stay compared with those with a score < 3 (8.0 [6.0-10.0] vs 6.5 [4.0-9.0] d, respectively, P = .007). CONCLUSION: The AECOPD-F score could accurately predict stay in hospitalized COPD subjects. The implementation of this score in clinical practice could be useful in the discharge planning of such subjects.

Collateral damage: depressive symptoms in the partners of COPD patients.

BACKGROUND: Depression is a frequent comorbidity in COPD patients and is associated with greater physical impairment, increased health-care utilization, and worse outcomes. The presence of depressive symptoms in the partners of COPD patients has not been evaluated. METHODS: We evaluated the partners of 230 consecutive COPD patients included in a prospective study. Depressive symptoms were evaluated using Beck's Depression Inventory (BDI) on the first day of admission for COPD exacerbation. Patients were followed-up for 1 year. RESULTS: Significant depressive symptoms were present in 39.6 % of the COPD patients and in 40.9 % of their partners. Beck scores were higher in the partners of patients with severe airflow obstruction and in those with ≥2 exacerbations and ≥1 hospitalizations for COPD exacerbation during the 1-year follow-up. The BDI score of the patients' partners was significantly correlated with the BDI score of the COPD patients (r s = 0.422). In multivariate analysis, depressive symptoms in the COPD patients were an independent predictor of depressive symptoms in their partners (OR 4.136, 95 % CI 1.991-8.594; p < 0.001). CONCLUSIONS: A large proportion of the partners of COPD patients present significant depressive symptoms. The identification of those patients and their partners represents a possible target for intervention.