ECFS standards of care on CFTR-related disorders: Identification and care of the disorders.

This is the third paper in the series providing updated information and recommendations for people with cystic fibrosis transmembrane conductance regulator (CFTR)-related disorder (CFTR-RD). This paper covers the individual disorders, including the established conditions - congenital absence of the vas deferens (CAVD), diffuse bronchiectasis and chronic or acute recurrent pancreatitis - and also other conditions which might be considered a CFTR-RD, including allergic bronchopulmonary aspergillosis, chronic rhinosinusitis, primary sclerosing cholangitis and aquagenic wrinkling. The CFTR functional and genetic evidence in support of the condition being a CFTR-RD are discussed and guidance for reaching the diagnosis, including alternative conditions to consider and management recommendations, is provided.

[CF Lung Disease - a German S3 Guideline: Pseudomonas aeruginosa].

Cystic Fibrosis (CF) is the most common autosomal recessive genetic multisystemic disease. In Germany, it affects at least 8000 people. The disease is caused by mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene leading to dysfunction of CFTR, a transmembrane chloride channel.

Pulmonary Aspergillosis in People with Cystic Fibrosis.

In the last decade, fungal respiratory diseases have been increasingly investigated for their impact on the clinical course of people with cystic fibrosis (CF), with a particular focus on infections caused by spp. The most common organisms from this genus detected from respiratory cultures are and , followed by , , and . These species have been identified to be both chronic colonizers and sources of active infection and may negatively impact lung function in people with CF.

Dynamics of abdominal symptoms during the start of a new therapy with elexacaftor/tezacaftor/ivacaftor using the novel CFAbd-day2day questionnaire.

Elexacaftor-tezacaftor-ivacaftor (ETI) is a novel, highly effective CFTR modulator combination proven to enhance lung function and body weight in people with cystic fibrosis (pwCF) carrying a F508del mutation. Recently, we revealed significant reductions in abdominal symptoms (AS) in German, British, and Irish pwCF after 24-26 weeks of ETI using the CFAbd-Score, the first patient-reported outcome measure (PROM) specifically developed and validated for pwCF following FDA guidelines. Notably, many pwCF reported marked changes in their AS during the first days of the new treatment.

Proliferative activity of antigen-specific CD154+ T cells against bacterial and fungal respiratory pathogens in cystic fibrosis decreases after initiation of highly effective CFTR modulator therapy.

Together with impaired mucociliary clearance, lung disease in cystic fibrosis (CF) is driven by dysregulation of innate and adaptive immunity caused by dysfunctional CFTR (Cystic Fibrosis Transmembrane Conductance Regulator), leading to airway infection and hyperinflamma-tion. The highly effective CFTR modulator therapy (HEMT) elexacaftor/tezacaftor/ivacaftor (ETI) generates substantial improvements in clinical outcomes of people with CF (pwCF) by restoration of CFTR activity. Aberrant immune responses of lymphocytes due to CFTR dysfunction has been described in the past, but not the effects of CFTR restoration by HEMT on these cells.

Corrigendum: Elexacaftor-Tezacaftor-Ivacaftor treatment reduces abdominal symptoms in cystic fibrosis-early results obtained with the CF-specific CFAbd-Score.

[This corrects the article DOI: 10.3389/fphar.2022.

Antibiotic Therapy for Pulmonary Exacerbations in Cystic Fibrosis-A Single-Centre Prospective Observational Study.

People with cystic fibrosis experience bronchopulmonary exacerbations, leading to lung damage, lung function decline, increased mortality, and a poor health-related quality of life. To date, there are still open questions regarding the rationale for antibiotic use and the optimal duration of antibiotic therapy. This prospective single-center study (DRKS00012924) analyzes exacerbation treatment over 28 days in 96 pediatric and adult people with cystic fibrosis who started oral and/or intravenous antibiotic therapy in an inpatient or outpatient setting after clinician diagnosis of bronchopulmonary exacerbation.

Antigen specificity and cross-reactivity drive functionally diverse anti-Aspergillus fumigatus T cell responses in cystic fibrosis.

BACKGROUNDThe fungus Aspergillus fumigatus causes a variety of clinical phenotypes in patients with cystic fibrosis (pwCF). Th cells orchestrate immune responses against fungi, but the types of A. fumigatus-specific Th cells in pwCF and their contribution to protective immunity or inflammation remain poorly characterized.

Elexacaftor-Tezacaftor-Ivacaftor Treatment Reduces Abdominal Symptoms in Cystic Fibrosis-Early results Obtained With the CF-Specific CFAbd-Score.

The novel and highly effective CFTR modulator combination of elexacaftor-tezacaftor-ivacaftor (ETI) has been shown to improve lung function and body weight in people with Cystic Fibrosis (pwCF) carrying a F508del mutation. However, the impact of these modulators on gastrointestinal (GI) symptoms is relatively unknown. Therefore, the CFAbd-Score was developed and validated following FDA recommendations for development of a PROM including focus groups, multidisciplinary CF specialists, people with CF and their families.

Genetic diversification of persistent within cystic fibrosis patients.

(.) infections in Cystic Fibrosis (CF) patients cause a deterioration of lung function. Treatment of these multidrug-resistant pathogens is associated with severe side-effects, while frequently unsuccessful.

Clinician variability in the diagnosis and treatment of aspergillus fumigatus-related conditions in cystic fibrosis: An international survey.

Background: The diagnosis and treatment of Aspergillus fumigatus (Af)-related conditions remain a challenge in cystic fibrosis (CF) due to overlapping features of disease and absence of clinical guidelines for Af-related conditions outside of ABPA.

Objective: To investigate the differences of clinical practice in the diagnosis and management of Af-related conditions in CF.

Methods: We conducted an international survey to CF clinicians to ascertain the screening, diagnostic, and treatment practices for Af-related conditions in CF.

Emerging Fungal Threats in Cystic Fibrosis.

In the past three decades, fungal respiratory colonization and fungal respiratory infections increasingly raised concern in cystic fibrosis (CF). Reasons for this are a better knowledge of the pathogenicity of fungi, whereby detection is sought in more and more CF centers, but also improvement of detection methods. However, differences in fungal detection rates within and between geographical regions exist and indicate the need for standardization of mycological examination of respiratory secretions.

Clinical impact of levofloxacin inhalation solution in cystic fibrosis patients in a real-world setting.

Background: Levofloxacin inhalation solution is the most recently approved inhaled antibiotic in Europe and Canada for adult cystic fibrosis patients. Its efficacy and safety have been assessed in randomized controlled trials. Our aim was to evaluate real life experience and outcomes in our treatment centre.

Frequent Pet Contact as Risk Factor for Allergic Bronchopulmonary Aspergillosis in Cystic Fibrosis.

() frequently colonizes the respiratory tract of patients with cystic fibrosis (CF). is associated with loss of pulmonary function and allergic bronchopulmonary aspergillosis (ABPA), a hypersensitivity fungal lung disease. Environmental factors have impact on CF patients' lung function variation.

Prospective Evaluation of -Specific IgG in Patients With Cystic Fibrosis.

Background: In Cystic Fibrosis (CF), the airways are often colonized by opportunistic fungi. The most frequently detected mold is (). diseases are associated with significant morbidity and mortality.

Urban Life as Risk Factor for Aspergillosis.

() frequently colonizes the airways of patients with cystic fibrosis (CF) and can cause severe diseases, such as allergic bronchopulmonary aspergillosis, bronchitis or even pneumonia. However, risk factors, including environmental factors, for acquiring in the respiratory tract of patients with CF are rarely studied and described. The aim of this study was to investigate whether urban or rural life could affect colonization with in the respiratory tract of patients with CF.

Risk factors for respiratory Aspergillus fumigatus in German Cystic Fibrosis patients and impact on lung function.

Airway inflammation and chronic lung infections in cystic fibrosis (CF) patients are mostly caused by bacteria, e.g. Pseudomonas aeruginosa (PA).

[Therapy of cystic fibrosis - new drugs give hope].

For decades there were only symptom-oriented therapies for the monogenetic disease cystic fibrosis. With the new modulator therapies there are new hopes to better influence the course of the disease, which has its manifestation in several organs such as the lungs, the liver or pancreas.In addition to ivacaftor, lumacaftor/ivacaftor and tezacaftor/ivacaftor, a triple combination with elexacaftor/tezacaftor/ivacaftor was developed.

Gene-Dose Effect of Gain-of-Function Mutations Determines Neutrophil Activation in Familial Mediterranean Fever.

Familial Mediterranean fever (FMF) is caused by mutations within the Mediterranean fever () gene. Disease severity depends on genotype and gene dose with most serious clinical courses observed in patients with M694V homozygosity. Neutrophils are thought to play an important role in the initiation and perpetuation of inflammatory processes in FMF, but little is known about the specific characteristics of these cells in FMF patients.

Human Anti-fungal Th17 Immunity and Pathology Rely on Cross-Reactivity against Candida albicans.

Th17 cells provide protection at barrier tissues but may also contribute to immune pathology. The relevance and induction mechanisms of pathologic Th17 responses in humans are poorly understood. Here, we identify the mucocutaneous pathobiont Candida albicans as the major direct inducer of human anti-fungal Th17 cells.

[Patients with cystic fibrosis become adults : Treatment hopes and disappointments].

Mucoviscidosis or cystic fibrosis (CF) is one of the most frequent monogenetic diseases in middle Europe. It is inherited in an autosomal recessive manner. A defect in the cystic fibrosis transmembrane conductance regulator (CFTR) channel reduces chloride ion transport to the cell membrane, which leads to malfunctions in all exocrine glands.