Associations between respiratory pathogens and lung function in primary ciliary dyskinesia: cross-sectional analysis from the PROVALF-PCD cohort.

Introduction: Respiratory pathogens are frequently isolated from airway samples in primary ciliary dyskinesia (PCD) patients. Few studies have investigated associations between these pathogens and lung function, with current management based on evidence from cystic fibrosis. We investigated the association between commonly isolated respiratory pathogens and lung function in PCD patients. Methods: Using a cross-sectional design, we prospectively collected clinical and concurrent microbiology data from 408 participants with probable or confirmed PCD, aged ≥5 years, from 12 countries. We used Global Lung Function Initiative 2012 references to calculate forced expiratory volume in 1 s (FEV1) z-scores. For 351 patients (86%) with complete data, we assessed the association of the four most frequently isolated pathogens with lung function by fitting multilevel linear models with country as random intercept, adjusted for age at diagnosis, age at lung function, use of antibiotic prophylaxis and body mass index z-scores. Results: Individuals with Pseudomonas aeruginosa growth in culture had significantly lower FEV1 z-scores (ß= -0.87, 95% CI -1.40- -0.34), adjusted for presence of Haemophilus influenzae, methicillin-sensitive Staphylococcus aureus and Streptococcus pneumoniae, and for covariates. When stratified by age, associations remained strong for adults but not for children. Results were similar when ciliary defects by transmission electron microscopy were included in the models and when restricting analysis to only confirmed PCD cases. Conclusions: We found that P. aeruginosa was associated with worse lung function in individuals with PCD, particularly adults. These findings suggest that it is prudent to aim for P. aeruginosa eradication in the first instance, and to treat exacerbations promptly in colonised patients.

Pediatric airway compression in aortic arch malformations: a multidisciplinary approach.

Background: Aortic arch malformations (AAMs) should be suspected in the presence of persistent respiratory symptoms despite medical treatment or feeding problems at the pediatric age. Aim: We report a descriptive cohort of patients with AAMs and the local management protocol applied. Methods: A total of 59 patients with AAM were retrospectively reviewed. Three groups were identified: double aortic arch (DAA), group 1; complete vascular ring (non-DAA), group 2; and anomalous origin of the innominate artery (IA), group 3. Results: Prenatal diagnosis was available for 62.7% of the patients. In all, 49.2% of children were symptomatic. There was a significantly different prevalence of respiratory symptoms within the three groups: 73.7% in group 1, 24.2% in group 2, and 100% in group 3 (p-value: <0.001). Surgery was considered in the presence of symptoms in patients with DAA and in those with reduction of the tracheal section area greater than 50%. A total of 52.5% of the patients underwent surgical repair (median age 6 months). The median follow-up interval was 21.9 months. Respiratory symptoms improved in most symptomatic patients. Conclusions: No specific protocols are available for the management of patients with AAMs. Conservative treatment seems to be reasonable for asymptomatic patients or those with airway stenosis less than 50%. A close follow-up is necessary to identify early patients who become symptomatic.

Retrocardiac Pneumomediastinum: Description of an Unusual Case and Review of Literature.

Retrocardiac pneumomediastinum (RP) is the consequence of air trapping in the inferior and posterior mediastinum. It is characterized by the presence of a right or left para-sagittal infrahilar oval or pyramidal air collection on a chest X-ray. It is usually detected in neonates because of alveolar rupture after invasive ventilation or invasive manoeuvres applied on airways or the digestive tract. A healthy child came to the emergency department (ED) for acute respiratory failure due to viral bronchiolitis when he was 2 months old. Because of his clinical condition, he underwent helmet continuous positive airway pressure (HCPAP). When the condition allowed, he was discharged and sent home. He was re-admitted into the hospital for asthmatic bronchitis 3 months later. A frontal chest X-ray taken during the second hospitalization showed an oval-shaped retrocardiac air lucency not previously detected. Differential diagnosis including digestive and lung malformations was made. Finally, the diagnosis of RP was made. We report an unusual case of retrocardiac pneumomediastinum in a 5-month-old male infant after the application of continuous positive pressure via a helmet. RP presentation after the administration of non-invasive ventilatory support beyond the neonatal age is unusual. Although surgical drainage is curative, conservative treatment can be considered in hemodynamically stable patients.

Severe asthma guidelines in children and adolescents: A practical document for physicians.

Asthma is a common disease in childhood with a minority of affected children suffering from severe asthma. Patients with severe asthma require high dose inhaled glucocorticoids plus a second controller and/or systemic corticosteroids to be well-controlled or remain uncontrolled despite such treatment. Although only a small subset of children and adolescents falls in this category, the management of affected patients represents a major concern for pediatricians. Guidelines and recommendations have been designed to guide the management of this group of patients. Though the terms "recommendations" and "guidelines" are often used interchangeably, it should be noted that the first one should be used more narrowly to identify specific actions and the second one to broadly refer to the umbrella under which multiple recommendations for a specific condition are provided. Moreover, the availability of several and sometimes-conflicting documents on severe asthma management both in adult and pediatric age could generate confusion among health care professionals. The manuscript analyses seven papers addressing severe asthma, comparing any key aspects and differences. Finally, we tried to create a more practical document for physicians to simplify the interpretation of the several available documents on severe asthma management focusing the pediatric age.

Long term respiratory morbidity in patients with vascular rings: a review.

Abnormalities in position and/or branching of the aortic arch can lead to vascular rings that may cause narrowing of the tracheal lumen due to external compression, or constriction of the oesophagus, causing symptoms that vary in relation to the anatomical vascular pattern and the relationship between these structures. Respiratory morbidity related to external airways compression is a major concern in children affected by vascular rings. Clinical presentation depends on the severity of the tracheal lumen reduction and the presence of associated tracheomalacia. Recurrent respiratory infections, wheezing, atelectasis, and hyperinflation are mostly reported. As they are nonspecific and therefore difficult to recognize, attention should be given to all children with history of respiratory distress, extubation failure, noisy breathing, and recurrent respiratory infections. Early diagnosis and referral to specialized centres can prevent the long-term complications and improve the respiratory outcomes of these patients.

Primary ciliary dyskinesia: A multicenter survey on clinical practice and patient management in Italy.

INTRODUCTION: There are no recent data on primary ciliary dyskinesia (PCD) distribution, diagnosis and treatment in Italy. METHODS: A descriptive study based on a survey questionnaire. It consisted of three sections (patients, diagnosis, and treatment), and sent to all the Italian PCD Centers. RESULTS: Questionnaires obtained from 20/22 centers in 12/20 regions showed that the total number of PCD patients treated at the participating centers was of 416. Out of all centers, 55% follow <20 patients, two centers have >40 patients, and 75% follow both pediatric and adults. Age at diagnosis was between 4 and 8 years in 45% of the centers, <3 years in three centers. Nasal nitric oxide, transmission electron microscopy and ciliary high-speed video microscopy are performed in 75%, 90%, and 40% of centers, respectively. Immunofluorescence is available in five centers. Genetic analysis is offered in 55% of the centers, and in seven centers >50% of the patients have a known genetic profile. Patients treated at all centers receive inhaled saline solutions, corticosteroids and chest physiotherapy. Prophylactic antibiotics and mucolytics are prescribed in 95% and 50% of the centers, respectively. Pseudomonas infection is treated with oral or inhaled antibiotics. CONCLUSIONS: Many Italian centers care for a small number of pediatric and adult patients, and diagnosis is often delayed. We found a great variability in the available diagnostic procedures, as well in the prescribed therapies. Our study will help to uniform diagnostic algorithm and share treatments protocols for PCD in Italy and allowed to set specific national goals.

Comparison of mental health in individuals with primary ciliary dyskinesia, cystic fibrosis, and parent caregivers.

INTRODUCTION: Individuals with chronic respiratory diseases and caregivers are at higher risk for depression and anxiety. Primary ciliary dyskinesia (PCD) and cystic fibrosis (CF) are both rare genetic diseases, characterized by recurrent respiratory infections. This study compared depression and anxiety in people with PCD (pwPCD) and CF (pwCF), and caregivers, using the screening tools recommended in the CF guidelines. METHODS: Patient Health Questionnaire (PHQ-9) and Generalized Anxiety Disorder (GAD-7) were administered to a PCD and CF sample. Given that PCD is extremely rare, they were matched on age and sex to pwCF at a 1:2 ratio. Similar procedures were performed with parents. RESULTS: A total of 63 patients and 129 caregivers participated: 21 pwPCD and 42 pwCF (ages 12-34 years) plus 43 caregivers of pwPCD and 86 caregivers of pwCF. A high percentage of patients scored above the cut-off for depression (PCD: 33%; CF: 43%) and anxiety (PCD and CF both: 43%), mostly mild. Similarly, a high percentage of caregivers scored above the cut-off for depression (PCD: 42-54%; CF: 45-46%) and anxiety (PCD: 47-54%; CF: 39-56%). Suicidal ideation was endorsed by 9.5% of pwPCD, 20% of mothers and 10% of fathers and 5% of pwCF, 3% of mothers, but no fathers. CONCLUSION: A large percentage of patients and caregivers reported elevated psychological distress and suicidal ideation. Addressing psychological symptoms is critical given they are associated with poor adherence, missed clinic visits, increased inflammation and worse quality of life. Mental health screening and treatment should be integrated into PCD care.

Noncystic fibrosis bronchiectasis in children and adolescents: Follow-up over a decade.

BACKGROUND: Noncystic fibrosis bronchiectasis (NCFB) is still considered an "orphan disease" in pediatric age. OBJECTIVE: The study describes the clinical and functional features, the instrumental, and microbial findings of a large cohort of patients with NCFB, followed in a single tertiary level hospital. METHODS: Children and adolescents diagnosed with NCFB from January 1, 2010 to December 31, 2019 were included. Data from the diagnosis and during the years of follow-up were recorded retrospectively. RESULTS: One hundred and thirty-eight patients were enrolled. The most common cause of NCFB was postinfectious (33%), followed by primary ciliary dyskinesia (PCD) (30%), esophageal atresia (EA) (9.5%), and secondary immunodeficiency (9.5%). Chronic cough was the most frequent symptom. The median age of symptoms presentation was 3 years (interquartile age [IQR]: 12-84), with a precocious onset in PCD and EA groups. The median age of CT diagnosis was 9 years for all groups but PCD patients who were diagnosed at older age. Lingula, medium, upper, and lower lobes were more involved in PCD group, while diffuse distribution was observed in the postinfectious one. Microbial exams showed Pseudomonas aeruginosa colonization higher in PCD patients (22%). Despite microbial differences in airways colonization, no difference in respiratory exacerbation rate was recorded among groups. Lung function tests demonstrated the stability of forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) over time, except for the secondary immunodeficiency group. CONCLUSIONS: The role of infections in developed countries should not be underestimated and a major effort to obtain an earlier identification of bronchiectasis should be taken. A prompt diagnosis of NFCB could help to reduce the frequency of exacerbations and improve the stability of lung function over time.

Effects of the COVID-19 pandemic and lockdown on symptom control in preschool children with recurrent wheezing.

INTRODUCTION: Preschool wheezers are at high risk of recurrent attacks triggered by respiratory viruses, sometimes exacerbated by exposure to allergens and pollution. Because of the COVID-19 infection, the lockdown was introduced, but the effects on preschool wheezers are unknown. We hypothesized that there would be an improvement in outcomes during the lockdown, and these would be lost when the lockdown was eased. MATERIALS AND METHODS: Patients underwent medical visits before and after the COVID-19 lockdown. We recorded the childhood Asthma Control Test (cACT) and a clinical questionnaire. Data on symptoms, the need for medications and the use of healthcare resources were recorded. We compared these data with retrospective reports from the preceding year and prospectively acquired questionnaires after lockdown. RESULTS: We studied 85 preschool wheezers, mean age 4.9 years. During the lockdown, cACT score was significantly higher (median 25 vs. 23); families reported a dramatic drop in wheezing episodes (51 vs. none), significant reductions in the day and nighttime symptoms, including episodes of shortness of breath (p < .0001); the use of salbutamol and oral corticosteroids (OCS) dropped significantly (p < .0001) and 79 (95%) patients needed no OCS bursts during the lockdown. Finally, patients had significantly fewer extra medical examinations, as well as fewer Emergency Room visits (p < .0001). All were improved compared with the same time period from the previous year, but outcomes worsened significantly again after lockdown (cACT median: 22). CONCLUSIONS: During the national lockdown, children with persistent preschool wheeze showed a significant clinical improvement with reduction of respiratory symptoms, medication use for exacerbations, and use of healthcare resources. This trend reversed when lockdown restrictions were eased.

Difficult and Severe Asthma in Children.

Asthma is the most frequent chronic inflammatory disease of the lower airways affecting children, and it can still be considered a challenge for pediatricians. Although most asthmatic patients are symptom-free with standard treatments, a small percentage of them suffer from uncontrolled persistent asthma. In these children, a multidisciplinary systematic assessment, including comorbidities, treatment-related issues, environmental exposures, and psychosocial factors is needed. The identification of modifiable factors is important to differentiate children with difficult asthma from those with true severe therapy-resistant asthma. Early intervention on modifiable factors for children with difficult asthma allows for better control of asthma without the need for invasive investigation and further escalation of treatment. Otherwise, addressing a correct diagnosis of true severe therapy-resistant asthma avoids diagnostic and therapeutic delays, allowing patients to benefit from using new and advanced biological therapies.

A Novel, Portable MESH Nebulizer-An Alternative to Metered Dose Inhaler: Efficacy and Usability in Preschool Wheezers.

Introduction and Objectives: Wheezing episodes are the first causes of doctor's consultation in preschool age. Treatment is usually administered with a metered dose inhaler (MDI) spacer. At variance, many parents and doctors prefer to use a compressor nebulizer, which cannot be easily carried. The study is aimed at testing whether a pocket mesh nebulizer has similar efficacy and acceptability than a standard MDI device. Materials and Methods: The IPAC study was a randomized, controlled, non-inferiority trial (number: 1616/2018, Ospedale Pediatrico Bambino Gesu'-IRCCS). The study had two arms: cases, using MicroAIR U100, and controls, using MDI+spacer device. Both devices were adopted for long-term treatment and for exacerbations. Follow-up was organized with clinical visits and a daily e-diary connected to an application for mobile phone. Results: One hundred patients were enrolled. The frequency of asthmatic symptoms showed a non-inferiority for MicroAIR U100 group vs. MDI. Accordingly, no significant difference was found in the average % of days with cough, wheezing, breathlessness after exercise, days lost at school, and not-programmed visits. Considering only patients with >1 day with symptoms, no significant sdifferences were found in the number of exacerbations nor in the cumulative days with symptoms. The acceptance and usability of both devices have been favorable. However, the MDI+AeroChamber® device showed better acceptability. Conclusions: Our study shows that MicroAIR U-100, a mesh nebulizer, has similar clinical efficacy but lower acceptance and usability than an MDI plus Aerochamber® in delivering therapy in preschool wheezers. Therefore, MicroAIR U-100 might be a valuable second choice, when the delivery of medication with an MDI plus Aerochamber® is not accepted, or wrongly used by the parents.

Allergic rhinoconjunctivitis.

Allergic rhinitis (AR) is induced by an IgE-mediated immune reaction after allergen exposure. The typical symptoms are itching, nasal discharge, sneezing and nasal obstruction. The diagnosis is based on the concordance between allergic symptoms and diagnostic tests. The skin prick test (SPT) is recommended as the "gold standard" method. First generation H1-antihistamines are widely used for treatment of AR. Intranasal glucocorticosteroids are well tolerated and can be used also in paediatric age. Allergic rhinitis cannot be considered as an isolated pathology. Other atopic diseases (allergic conjunctivitis, atopic eczema, asthma) are commonly associated.

The Role of Vitamin D in Allergic Diseases in Children.

The role of vitamin D in calcium and phosphate homeostasis is well known; however, in addition to traditional functions, vitamin D modulates a variety of processes, and evidence shows that it has an important role in different allergic diseases such as asthma, atopic dermatitis, and food allergy. Vitamin D acts by binding to the vitamin D receptor, which is present in a variety of tissues; for this reason it is considered a hormone. One of the most important functions is to modulate the immune system response, both innate and adaptive, by suppressing Th2-type response and increasing natural killer cells. Recent studies show that higher serum levels of 25-hydroxyvitamin D were associated with a reduced risk for asthma exacerbations and hospitalization. Other experimental data suggest that vitamin D can potentially increase the therapeutic response to glucocorticoid and potentially be used as an add-on treatment in steroid-resistant asthmatic patients. However, vitamin D stimulates the production and regulation of skin antimicrobial peptides, such as cathelicidins, which have both direct antimicrobial activity and induced host cellular response by triggering cytokine release. Recent evidence suggests that low blood vitamin D level is a risk factor for food allergy; vitamin D deficiency predisposes to gastrointestinal infections, which may promote the development of food allergy. In conclusion, several data suggest that serum 25-hydroxyvitamin D levels are often insufficient in children with asthma, atopic dermatitis, and food allergy. Further clinical trials are needed to provide conclusive evidence and to identify the effects of vitamin D in allergic diseases.