Cystic fibrosis (CF), the most common genetically inherited disease in Caucasian populations, is a multi-systemic life-threatening autosomal recessive disorder caused by mutations in the cystic ...fibrosis transmembrane conductance regulator (CFTR) gene. In 2012, the arrival of CFTR modulators (potentiators, correctors, amplifiers, stabilizers, and read-through agents) revolutionized the therapeutic approach to CF. In this review, we examined the physiopathological mechanism of chronic dysregulated innate immune response in the lungs of CF patients with pulmonary involvement with particular reference to phagocytes, critically analyzing the role of CFTR modulators in influencing and eventually restoring their function. Our literature review highlighted that the role of CFTR in the lungs is crucial not only for the epithelial function but also for host defense, with particular reference to phagocytes. In macrophages and neutrophils, the CFTR dysfunction compromises both the intricate process of phagocytosis and the mechanisms of initiation and control of inflammation which then reverberates on the epithelial environment already burdened by the chronic colonization of pathogens leading to irreversible tissue damage. In this context, investigating the impact of CFTR modulators on phagocytic functions is therefore crucial not only for explaining the underlying mechanisms of pleiotropic effects of these molecules but also to better understand the physiopathological basis of this disease, still partly unexplored, and to develop new complementary or alternative therapeutic approaches.
Patients with cystic fibrosis (CF) are prone to malnutrition and growth failure, mostly due to malabsorption caused by the derangement in the chloride transport across epithelial surfaces. Thus, ...optimal nutritional care and support should be an integral part of the management of the disease, with the aim of ameliorating clinical outcomes and life expectancy. In this report, we analyzed the nutrition support across the different ages, in patients with CF, with a focus on the relationships with growth, nutritional status, disease outcomes and the use of the CF transmembrane conductance regulator (CFTR) modulators. The nutrition support goal in CF care should begin as early as possible after diagnosis and include the achievement of an optimal nutritional status to support the growth stages and puberty development in children, that will further support the maintenance of an optimal nutritional status in adult life. The cornerstone of nutrition in patients with CF is a high calorie, high-fat diet, in conjunction with a better control of malabsorption due to pancreatic enzyme replacement therapy, and attention to the adequate supplementation of fat-soluble vitamins. When the oral caloric intake is not enough for reaching the anthropometric nutritional goals, supplemental enteral feeding should be initiated to improve growth and the nutritional status. In the last decade, the therapeutic possibilities towards CF have grown in a consistent way. The positive effects of CFTR modulators on nutritional status mainly consist in the improvement in weight gain and BMI, both in children and adults, and in an amelioration in terms of the pulmonary function and reduction of exacerbations. Several challenges need to be overcome with the development of new drugs, to transform CF from a fatal disease to a treatable chronic disease with specialized multidisciplinary care.
In the last 20 years, gut microbiota in patients with cystic fibrosis (CF) has become an object of interest. It was shown that these patients had gut dysbiosis and this could explain not only the ...intestinal manifestations of the disease but also part of those involving the respiratory tract. The acquisition of previously unknown information about the importance of some bacteria, i.e., those partially or totally disappeared in the gut of CF patients, in the regulation of the activity and function of the gut and the lung was the base to suggest the use of probiotics in CF patients. The main aim of this paper is to discuss the biological basis for probiotic administration to CF patients and which results could be expected. Literature analysis showed that CF intestinal dysbiosis depends on the same genetic mutations that condition the clinical picture of the diseases and is aggravated by a series of therapeutic interventions, such as dietary modifications, the use of antibiotics, and the administration of antacids. All this translates into a significant worsening of the structure and function of organs, including the lung and intestine, already deeply penalized by the genetic alterations of CF. Probiotics can intervene on dysbiosis, reducing the negative effects derived from it. However, the available data cannot be considered sufficient to indicate that these bacteria are essential elements of CF therapy. Further studies that take into account the still unsolved aspects on how to use probiotics are absolutely necessary.
To describe the symptoms and clinical course of SARS-CoV-2 infection in patients with cystic fibrosis (CF).
We carried out a prospective multicentre cohort study based on 32 CF centres and 6597 ...patients. Centres were contacted to collect baseline and follow-up data of patients who reported symptoms suggestive of COVID-19 or who had contact with a positive/suspected case between the end of February and July 2020. Symptoms and clinical course of the infection were compared between patients who tested positive by molecular testing (cases) and those who tested negative (controls).
Thirty patients were reported from the centres, 16 of them tested positive and 14 tested negative. No differences in symptoms and outcome of the disease were observed between groups. Fever, cough, asthenia and dyspnea were the most frequently reported symptoms. Eight cases (50%) were hospitalized but none required ICU admission. Two adults with a history of lung transplant required non-invasive ventilation, none required ICU admission and all patients fully recovered without short-term sequelae.
The course of SARS-CoV-2 in our patients was relatively favorable. However, COVID-19 should not be considered a mild disease in CF patients, particularly for those with severely impaired respiratory function and organ transplant.
In 102 healthy Caucasians, 20–50 years old, we investigated the effect of anthropometrics on the 6-min walk test (6MWT), in order to provide reference values for walk distance (6MWD), oxygen ...saturation (SpO
2), pulse rate (PR), respiratory rate (RR), breathlessness perception (VAS) and for the walking distance and body weight product (
DW).
The mean 6MWD and
DW values were 593±57 and 638±44
m (
P<0.01) and 35,030±5306 and 48,882±6555
kg
m (
P<0.01), respectively for women and for men. While walking, SpO
2 remained unaltered and subjects reached 67±10% of their maximal predicted heart rate and a RR mean value of 19±4
bpm. VAS ratings were significantly higher in females as compared to males (24±15 vs. 18±5
mm,
P<0.05), however, when corrected for PR change while walking, they were not different. The equation by stepwise multiple regression analysis included height, age and gender for the 6MWD and accounted for 42% of the total variance.
This study confirms the relevant effect of anthropometrics on walking capacity and suggests that when rating dyspnea, the change in heart rate during walking should be considered.
Cystic fibrosis (CF) is the most common life-limiting inherited disease in Caucasian populations, affecting approximately 80,000 people worldwide. CF is a complex multi-organ monogenic autosomal ...recessive disorder caused by a mutation in cystic fibrosis transmembrane conductance regulator (CFTR) gene. Since the discovery of the CFTR gene in 1989, more than 2000 mutations have been identified so far and about 240 can cause CF. Until recently, the treatment for CF was aimed to prevent and manage the manifestations of CFTR dysfunction, primarily recurrent pulmonary infections and pancreatic exocrine failure. Over the past few decades, the therapeutic approach to CF has been revolutionized by the development of a new class of small molecules called CFTR modulators that target specific defects caused by mutations in the CFTR gene. CFTR modulators have been shown to change profoundly the clinical course of the CF, leading to meaningful improvements in the lives of a large proportion of people of CF heterozygous for F508del, especially if started in young children. Further studies are needed to extend the use of triple CFTR modulation therapy also for young children in order to prevent the irreversible effects of the disease and for patients with very rare mutations with a personalized approach to treatment.
In recent years, advances in diagnosis and treatment have significantly modified the short- and long-term prognosis of cystic fibrosis (CF) patients. However, as in the past, the most important ...health problem that has significantly reduced the quality of life in CF patients is the progressive deterioration of lung structure and function. In recent years, Achromobacter species have emerged with increasing incidence in the respiratory secretions of CF subjects. The significance of this detection remains debated. In this review article, the characteristics of these pathogens, the importance of their presence in CF patients, and possible antibiotic treatment of treatments for colonization and infection are discussed. Literature analysis shows that Achromobacter species, mainly A. xylosoxidans, are pathogens with intrinsic characteristics that favour persistent lung colonization and several virulence factors and secretion systems that significantly interfere with respiratory cell survival. However, although it seems undebatable that Achromobacterspecies detection is a marker of CF severity, the role of these pathogens as a cause of lung structure and functional deterioration is not definitively established. Nonetheless, there is general agreement about the need for antibiotic therapy to eradicate these pathogens when they are detected in CF patients. Unfortunately, eradication is difficult, and no standard treatment is recommended by scientific societies. New possibilities are potentially offered by some recently developed drugs, such as cefiderocol, but further studies on the dosage, treatment duration and efficacy and safety of this new antibiotic in CF patients of different ages are urgently needed.
The care of cystic fibrosis (CF) traditionally consists of regular visits to the clinic where a multidisciplinary team can visit the patient, adjust treatments and monitor the disease. During the ...COVID-19 pandemic when access to hospitals and medical environments was very limited, the role of telemedicine was crucial to keep in touch with patients with chronic diseases such as CF. Increasing evidence demonstrates that electronic health can successfully support healthcare professionals in the management of people with CF. The use of devices connected to digital platforms or smartphones results in a continuous flow of data that can be shared with the clinician and the team in order to improve the knowledge of patients' diseases and the level of care needed. This narrative review aims to describe the application of telemedicine in CF disease with pros and cons. A literature analysis showed that telemedicine has several advantages in the management of patients with CF. With the evolving support of digital technology, telemedicine can promote clinical visits, adherence to daily treatment, including respiratory physiotherapy and physical exercise, early identification of pulmonary exacerbations and management of psychological issues. The main disadvantages are missed physical exam findings, lack of physical contact that can prevent conversation on sensitive topics, lack of access to technology and lack of technological skills. Furthermore, healthcare operators need appropriate training for telemedicine systems and need time to organise and analyse data generated remotely, which may increase the burden of daily work. Hybrid personalised care models that marge telemedicine and traditional care can be an ideal solution.
Respiratory viral infections represent the leading cause of hospitalization in infants and young children worldwide and the second leading cause of infant mortality. Among these, Respiratory ...Syncytial Virus (RSV) represents the main cause of lower respiratory tract infections (LRTIs) in young children worldwide. RSV manifestation can range widely from mild upper respiratory infections to severe respiratory infections, mainly bronchiolitis and pneumonia, leading to hospitalization, serious complications (such as respiratory failure), and relevant sequalae in childhood and adulthood (wheezing, asthma, and hyperreactive airways). There are no specific clinical signs or symptoms that can distinguish RSV infection from other respiratory pathogens. New multiplex platforms offer the possibility to simultaneously identify different pathogens, including RSV, with an accuracy similar to that of single polymerase chain reaction (PCR) in the majority of cases. At present, the treatment of RSV infection relies on supportive therapy, mainly consisting of oxygen and hydration. Palivizumab is the only prophylactic method available for RSV infection. Advances in technology and scientific knowledge have led to the creation of different kinds of vaccines and drugs to treat RSV infection. Despite the good level of these studies, there are currently few registered strategies to prevent or treat RSV due to difficulties related to the unpredictable nature of the disease and to the specific target population.
Cystic fibrosis (CF) is an autosomal recessive disorder, caused by genetic mutations in CF transmembrane conductance regulator protein. Several reports have indicated the presence of specific fatty ...acid alterations in CF patients, most notably decreased levels of plasmatic and tissue docosahexaenoic acid (DHA), the precursor of specialized pro-resolving mediators. We hypothesized that DHA supplementation could restore the production of DHA-derived products and possibly contribute to a better control of the chronic pulmonary inflammation observed in CF subjects. Sputum samples from 15 CF and 10 chronic obstructive pulmonary disease (COPD) subjects were collected and analyzed by LC/MS/MS, and blood fatty acid were profiled by gas chromatography upon lipid extraction and transmethylation. Interestingly, CF subjects showed increased concentrations of leukotriene B
(LTB
), prostaglandin E
(PGE
), and 15-hydroxyeicosatetraenoic acid (15-HETE), when compared with COPD patients, whereas the concentrations of DHA metabolites did not differ between the two groups. After DHA supplementation, not only DHA/arachidonic acid (AA) ratio and highly unsaturated fatty acid index were significantly increased in the subjects completing the study (
< 0.05) but also a reduction in LTB
and 15-HETE was observed, together with a tendency for a decrease in PGE
and an increase in 17-hydroxy-docosahexaenoic acid (17OH-DHA) levels. At the end of the washout period, LTB
, PGE
, 15-HETE, and 17OH-DHA showed a trend to return to baseline values. In addition, 15-HETE/17OH-DHA ratio in the same sample significantly decreased after DHA supplementation (
< 0.01) when compared with baseline. In conclusion, our results show here that in CF patients, an impairment in fatty acid metabolism, characterized by increased AA-derived metabolites and decreased DHA-derived metabolites, could be partially corrected by DHA supplementation.
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