Vitamin D deficiency in patients with cystic fibrosis: a systematic review and meta-analysis.

AIM: Vitamin D is a prominent modulator of immunity and respiratory function. It plays a vital role in respiratory diseases such as cystic fibrosis (CF). S. However, there is a dearth of information on patients with CF. The purpose of the meta-analysis is to highlight the importance of following the existing guidelines regarding maintenance of Vitamin D serum levels in patients with CF. METHODS: The systematic search was conducted without utilizing any time or language limitations in original database from the beginning until March 2022. The meta-analysis was performed using a random-effects model. Heterogeneity was determined by I2 statistics and Cochrane Q test. RESULTS: Pooled analysis using the random-effects model of the 8 case-control studies with 13 effect sizes revealed that the serum 25-OH-vitamin D in participants with cystic fibrosis was significantly lower than controls in pediatrics and adolescences (WMD: - 3.41 ng/ml, 95% CI - 5.02, - 1.80, p = < 0.001) and adults (WMD: - 2.60 ng/ml, 95% CI - 4.32, - 0.89, p = 0.003). Based on data from 12 studies (21 effect sizes) with a total of 1622 participants, the prevalence of vitamin D levels of 20-30 ng/ml in CF patients was 36% among pediatrics/adolescents and 63% among adults. In addition, 27% of pediatric/adolescent CF patients and 35% of adult CF patients had vitamin D levels of below 20 ng/ml. CONCLUSIONS: As a result, according to the existing guidelines, our results proved the need to pay attention to the level of vitamin D in these patients.

Fractional Exhalation Nitric Oxide (FeNO) changes in cystic fibrosis patients induced by compound honey syrup: a pretest-posttest clinical trial.

OBJECTIVE: To evaluate the effect of Persian medicine Syrup 'compound honey syrup (CHS)' on fractional exhalation nitric oxide (FENO) changes in patients with cystic fibrosis (CF). STUDY DESIGN: We conducted a before-after clinical trial on 70 CF patients. All patients received classical treatments for CF along with CHS (including honey, Ginger, cinnamon, saffron, cardamom and galangal), 5-10 cc (depending on the age and weight of patients) in 100 cc of warm boiled water twice a day, 30 min after meals. In this clinical trial, before and 12 weeks after the start of the CHS, FeNO test was evaluated. RESULTS: From 70 patients were enrolled, 44 patients completed this 12-week course of treatment. At the end of the study, changes in FeNO was significantly different before and after treatment (P-value < 0.05). At the end of the study, no dangerous side effects of CHS was reported. CONCLUSIONS: This study revealed that CHS can be effective as a complementary and safe drug in the medication of CF patients.

Combination of Serologic Tests and Sputum Culture Results as the Best Diagnostic Method of Pseudomonas aeruginosa Infection in Cystic Fibrosis Patients.

Background: One of the most common reasons for mortality in patients with cystic fibrosis (CF) is lung infections, among which Pseudomonas aeruginosa (Pa) infection has the largest share. Diagnosis of Pa can be assessed by various methods such as sputum culture results and IgG antibody level via measuring the specific anti-Pa antibodies. This study aimed to select the best predictive technique in the diagnosis of Pa in CF patients through spirometry, sputum culture, and serum IgG antibody levels. Materials and Methods: In this cross-sectional study, blood and sputum or pharyngeal samples were taken from 68 patients with cystic fibrosis. Because spirometry was not possible in all patients, 34 patients could do the spirometry. The samples were studied concerning Pa infection. The data including variables such as age, sex, and spirometry results were obtained. Then, in the serologic method, 3 serum-specific antibody levels were determined by enzyme-linked immune sorbent assay (ELISA). Results: The average age of children was 7.4 ± 5.6 (ranging from 0.5 to 23) years. Generally, the percentage of Pa infection increased in CF patients with higher ages. A statistically direct significant relationship was observed between the concentration of serum IgG antibodies in patients with CF and Pa-positive sputum culture results (p<0.05). Conclusion: Serum IgG antibodies against specific Pa antigens could be a diagnostic method against Pa infection, especially in patients who cannot expectorate. However, because of the positive and negative predictive value of both serum IgG antibody levels and the results of the sputum culture, we suggested that utilizing the combination of these methods could be beneficial in earlier diagnosis of Pa.

Pulmonary Involvement in Neuromuscular Diseases: A Review.

Neuromuscular diseases (NMDs) affect muscle function directly or indirectly by affecting nerves or neuromuscular junctions. One of the leading causes of death in patients with NMD is respiratory muscle weakness (RMW). Respiratory involvement in patients with NMD can manifest widely, from mild failure that may initially affect only sleep to severe failure that can be life-threatening. Care approaches include arranged and precise clinical follow-ups of signs of sleep-disordered breathing, daytime hypoventilation, coughing, and swallowing disturbances. This manuscript will review the mechanisms and abnormalities of respiratory function in patients with NMD and help optimize NMD management.

Evaluating the efficacy of inhaled amikacin as an adjunct to intravenous combination therapy (ceftazidime and amikacin) in pediatric cystic fibrosis pulmonary exacerbation.

Background: Pseudomonas aeruginosa is the most common microorganism found in the sputum culture of Cystic fibrosis (CF) patients causing the pulmonary destruction. Aminoglycosides have a low diffuse rate from lipid membranes, and respiratory system secretions. Regarding the burden of pulmonary exacerbation caused by the pseudomonas aeruginosa in cystic fibrosis patients in the long term and the limited number of clinical trials focused on appropriate treatment strategies, the present study evaluated the concurrent inhaled and intravenous aminoglycoside antibiotics for pulmonary exacerbation caused by the pseudomonas aeruginosa as a safe and effective treatment in children. Method: This study was a blinded, randomized clinical trial phase conducted in a tertiary referral pediatric teaching hospital from May 2021 to May 2022. The patients were randomly allocated to receive intravenously administered ceftazidime and Amikacin alone or with inhaled Amikacin. Forced expiratory volume (FEV1), Amikacin via the level, kidney function tests, audiometry, inflammatory markers (erythrocyte sedimentation rate and C-reactive protein), hospital stay, and bacterial eradication rate were compared in two therapy groups. Results: the average FEV1 has increased by 47% in Neb + group compared to Neb- group following treatment. Hospital stay was lower in Neb + group. No renal toxicity or ototoxicity was observed in both therapy groups. Pseudomonas aeruginosa eradication rate Neb- and Neb + groups were 44% and 69%, respectively (p-value = 0.15). Conclusion: Concurrent inhaled and intravenous Amikacin is safe and effective to treat Pseudomonas aeruginosa exacerbation in CF patients. Moreover, co-delivery antibiotics' route treatment increased the eradication rate. Although not statistically significant, never the less, it is clinically relevant. The intervention reduced the length of hospitalization in this group. Clinical Trial Registration: clinicaltrials.gov, identifier [IRCT20120415009475N10].

The association of fecal calprotectin and respiratory exacerbation in cystic fibrosis patients.

BACKGROUND: CF patients experience several episodes of pulmonary exacerbations and reduction in their lung function progressively. Lung function is not the only diagnostic index by physicians to decide if CF patients require antibiotic therapy following pulmonary exacerbations. Non-invasive fecal indicators are increasingly being used to assess intestinal inflammation. Calprotectin is the most extensively utilized fecal biomarker in recent CF researches. METHODS: In this longitudinal study, 30 CF patients (1-18 years) without current infectious gastroenteritis were recruited from Mofid Children's Hospital and Masih Daneshvari Hospital, Tehran, Iran. Then, fecal calprotectin levels were evaluated before treatment, two weeks after systemic antibiotic administration, as well as recurrence of pulmonary exacerbation after first post-hospital discharge. RESULTS: The initial fecal calprotectin level in CF patients receiving antibiotics was 651.13 ± 671.04, significantly decreasing two weeks after antibiotic therapy and following recurrence (171.81 ± 224.40, 607.93 ± 549.89, respectively; P < 0.01). Following systemic antibiotic treatment, the patient's respiratory and GI symptoms improved (P < 0.01). CONCLUSION: Our findings revealed that fecal calprotectin modifications are associated with CF pulmonary exacerbations and antibiotic treatment could reduce calprotectin levels. Therefore, the fecal calprotectin level could be considered as a diagnostic tool and an index to follow the response to treatment in CF pulmonary exacerbations.

Re-positive PCR of SARS-CoV-2 in health care persons during COVID-19 pandemic.

Reinfection rate with SARS-CoV-2 and degree of protection by the induced antibody after the first episode of the infection is not well known, so it makes a big dilemma for health care personnel (HCP) who work in the front line of combating SARS-CoV-2. In this study, we investigated the frequency of SARS-CoV-2 redetection among HCP after the initial onset of the infection in a children's hospital during one year. Out of 131 seropositive HCP, 13.7% of them were symptomatic and PCR positive during 74-360 days after first sampling. Analysis of demographic data of seropositive HCP showed a correlation between a higher number of family members, higher body mass index, and the existence of underlying diseases with SARS-CoV-2 redetection. In conclusion, reinfection is one of the important problems in the SARS-CoV-2 pandemic. Research on this topic can help us to find answers to questions for estimating the duration of human protection with produced immunity after the infection or vaccination.

Corneal opacification, an atypical presentation of cystic fibrosis: a case report and review of the literature.

BACKGROUND: Respiratory and gastrointestinal manifestations are the main causes of mortality and morbidity in cystic fibrosis. Although these symptoms are well recognized, ophthalmic involvement of cystic fibrosis secondary to vitamin A deficiency is uncommon and has been reported very rarely in the medical literature. CASE PRESENTATION: Here, we report a 2.5-year-old Iranian boy who presented with bilateral corneal xerosis and corneal opacity secondary to vitamin A deficiency related to cystic fibrosis malabsorption. CONCLUSION: Malabsorption of fat-soluble vitamins is a common presentation in cystic fibrosis, but corneal opacity secondary to vitamin A deficiency as the initial presentation of cystic fibrosis is a very rare manifestation of fat malabsorption. This highlights the importance of complete systemic examination besides ophthalmic examination in approaching a child with ophthalmic complaint.

Urinary System and Renal Involvement in Children With Cystic Fibrosis.

INTRODUCTION: A few data on the prevalence of renal involvement in cystic fibrosis and its spectrum in childhood is available. In the present study, we conducted a prospective study on children who had cystic fibrosis and evaluated their renal involvement. In fact, the aim of the study was to provide data on the clinical consequences of proper identification of kidney disease in a group of children with cystic fibrosis. METHODS: This prospective study was conducted on 55 consecutive patients with previous diagnosis of cystic fibrosis during a threeyear period and at least 3 months to over 5 years or more follow-up. The inclusion criteria was the diagnosis of cystic fibrosis which was made by clinical presentation of cystic fibrosis and laboratory results. Initially, patients' medical records were reviewed and relevant data were collected. A 24-hour urine collection (or a random urine sampling in very young infants) was used to assess crystalluria and renal function was evaluated by blood sampling. RESULTS: Totally, 55 patients with cystic fibrosis were admitted in two hospitals with the mean age of 8.22 ± 5.66 years. GFR totally reduced in 34.5%. The overall prevalence of hypercalciuria was estimated to be 60%, while hyperoxaluria, hypocitraturia, and hyperuricosuria in 41.8%, 24.5%, and 47.3%; respectively. CONCLUSION: Crystalluria is a common consequence of cystic fibrosis in childhood. The prevailing crystalluric finding includes hypercalciuria followed by hyperuricosuria, and hyperoxaluria. During disease GFR may be decreased due to several reasons such as nephrotoxic drugs usage.

Microbial contamination of home nebulizers in children with cystic fibrosis and clinical implication on the number of pulmonary exacerbations.

BACKGROUND: Early detection of pulmonary contamination in children with cystic fibrosis (CF) is essential since these children are vulnerable to Pseudomonas aeruginosa (P. aeruginosa) colonization. In Iran, home nebulization of antibiotics is a widespread practice in treatment for patients with CF and, to the best our knowledge, no bacteriological surveys have been conducted till date in this regard. METHOD: This observational, cross sectional study was conducted on 61 children with CF at Mofid Children's Hospital, Tehran, from September 2017 to march 2018. The swab sampling was performed from 61 home nebulizers used by children diagnosed with CF. Contemporaneous sputum sample or deep nasopharyngeal swab was taken from each patient for bacterial and fungal testing. Medical records of the patients were reviewed and the number of exacerbations were recorded over the last 12 months prior to the study enrollment. RESULTS: The results of study showed that, 43 (70.5%) nebulizers were contaminated; 31 (50.8%) mouthpieces, 21 (34.4%) reservoirs, and 11 (18%) connecting tubes. The most common organism to be isolated was P. aeruginosa and was recovered from 19 (31%) nebulizers, 16 of them belonged to patients chronically colonized with P. aeruginosa. The remaining three had at least one positive sputum culture for P. aeruginosa in the past 1 year before the study. There was a significant increase in the number of CF exacerbations with an average number of exacerbation being 1.5 ± 1(SD) over last 12 months in children who had pathogenic organisms recovered from their home nebulizers compared with 0.4 ± 0.7(SD) exacerbations per year in whom non-pathogenic organisms were isolated from their nebulizers (P < 0.001). CONCLUSION: The majority of domiciliary nebulizers used by children with CF were contaminated with microorganisms indicating that the nebulizers may serve as potential reservoirs of pathogens for the patients' lung. Perpetuating colonization is a possible concern in the ones recently colonized with P. aeruginosa and, therefore, decontamination of nebulizer requires more attention to prevent ongoing infection. The negative impact of contamination of nebulizer on CF exacerbation requires serious attention and further investigations.

Severe Combined Immunodeficiency: A Case Series and Review from a Tertiary Pediatric Hospital.

Severe combined immunodeficiency syndrome (SCID) is a life-threatening condition leading to early infant death as a result of severe infection, due to impaired cellular and humoral immune systems. Various forms of SCID are classified based on the presence or absence of T cells, B cells and natural killer cells. Patients usually present with recurrent infections and failure to thrive. Definitive treatment is hematopoietic stem cell transplantation. To achieve the best outcome, it should be performed prior to the development of severe infection. In This study, we described 10 patients (6 male and 4 female) with SCID who were admitted to Mofid Children Hospital, Tehran, Iran, from 2006 to 2013. We reviewed patients' clinical manifestation, laboratory data, family history and outcome. The mean age at the time of diagnosis was 131.8 days. One patient had non-consanguineous parents. Seven patients received BCG vaccine before the diagnosis of SCID, three of them showed disseminated BCG infection. One patient presented with invasive pulmonary aspergillosis. Flow cytometric analysis showed T⁻B⁺NK⁻ in three patients, T⁻B⁻NK⁺ in five patients, T⁻B⁻NK⁻ in one patient, and T⁻B⁺NK⁺ in one patient. This study highlights the importance of early diagnosis and patient referral before the occurrence of serious infection.

Auditory Brainstem Response Wave Amplitude Characteristics as a Diagnostic Tool in Children with Speech Delay with Unknown Causes.

Speech delay with an unknown cause is a problem among children. This diagnosis is the last differential diagnosis after observing normal findings in routine hearing tests. The present study was undertaken to determine whether auditory brainstem responses to click stimuli are different between normally developing children and children suffering from delayed speech with unknown causes. In this cross-sectional study, we compared click auditory brainstem responses between 261 children who were clinically diagnosed with delayed speech with unknown causes based on normal routine auditory test findings and neurological examinations and had >12 months of speech delay (case group) and 261 age- and sex-matched normally developing children (control group). Our results indicated that the case group exhibited significantly higher wave amplitude responses to click stimuli (waves I, III, and V) than did the control group (P=0.001). These amplitudes were significantly reduced after 1 year (P=0.001); however, they were still significantly higher than those of the control group (P=0.001). The significant differences were seen regardless of the age and the sex of the participants. There were no statistically significant differences between the 2 groups considering the latency of waves I, III, and V. In conclusion, the higher amplitudes of waves I, III, and V, which were observed in the auditory brainstem responses to click stimuli among the patients with speech delay with unknown causes, might be used as a diagnostic tool to track patients' improvement after treatment.

A survey on pulmonary pathogens and their antibiotic susceptibility among cystic fibrosis patients.

OBJECTIVE: This study was performed to investigate frequency and antimicrobial susceptibility of pulmonary pathogens in cystic fibrosis (CF) patients. METHODS: 129 pediatric patients with CF were enrolled in this cross-sectional study. Microbiological cultures were performed based on sputum or pharyngeal swabs. Antibiotic susceptibilities of the isolated bacteria were determined by the disk diffusion method. RESULTS: The main infecting pathogens were Pseudomonas aeruginosa (38.8%), Klebsiella pneumoniae (11.6%) and Staphyloccus areus (9.3%), respectively. The most active antibiotics included rifampin (91.7% susceptibility), vancomycin (85%) and imipenem (83.5%). Emerging resistance against aminoglycosides was observed. CONCLUSION: Regarding in vitro susceptibility results, cyclic treatment of long-term oral azithromycin and inhaled tobramycin could prophylactically be applied, and during exacerbations, imipenem or ceftazidime in combination with an aminoglycoside such as amikacin could be considered the drugs of choice.

Serum level of specific IgG antibody for aspergillus and its association with severity of asthma in asthmatic children.

Aspergillosis is one of the frequent causes of exacerbation of asthma depending on the geographical regions. The specific serum IgG level for aspergillus is a major diagnostic criterion in aspergillosis.Ninety-six asthmatic patients, with mean age of 5.4 ± 3.0 years who were referred to the asthma clinic of the Mofid Children's Hospital, were enrolled in this study. Serum specific IgG for aspergillus was measured and its association with severity of asthma was evaluated.Nineteen asthmatic patients (10 females and 9 males) had aspergillus IgG antibody. Among them, severe persistent asthma and moderate persistent asthma were detected in 5 and 13 cases, respectively, whereas only one patient suffered from mildpersistent asthma. A total of 36.5% of the 96 patients had a history of atopy, while 26% had allergic rhinitis. There was an association between the severity of asthma and the presence of aspergillus IgG antibody. Moreover, the positivity for aspergillus IgG antibody was higher in older patients.Our results indicated an association between aspergillus antibody level and severity of asthma. It could be recommended that the IgG titer for aspergillus is measured in pediatric patients with asthma, whereas co-morbidity of aspergillosis and asthma increases the risk of asthma exacerbation.

A survey on pulmonary pathogens and their antibiotic susceptibility among cystic fibrosis patients

OBJECTIVE:This study was performed to investigate frequency and antimicrobial susceptibility of pulmonary pathogens in cystic fibrosis (CF) patients. METHODS: 129 pediatric patients with CF were enrolled in this cross-sectional study. Microbiological cultures were performed based on sputum or pharyngeal swabs. Antibiotic susceptibilities of the isolated bacteria were determined by the disk diffusion method. RESULTS: The main infecting pathogens were Pseudomonas aeruginosa (38.8%), Klebsiella pneumoniae (11.6%) and Staphyloccus areus (9.3%), respectively. The most active antibiotics included rifampin (91.7% susceptibility), vancomycin (85%) and imipenem (83.5%). Emerging resistance against aminoglycosides was observed. CONCLUSION: Regarding in vitro susceptibility results, cyclic treatment of long-term oral azithromycin and inhaled tobramycin could prophylactically be applied, and during exacerbations, imipenem or ceftazidime in combination with an aminoglycoside such as amikacin could be considered the drugs of choice.

Impact of rhinitis on asthma control in children: association with FeNO.

BACKGROUND: The prevalence of rhinitis is high and frequently observed in association with asthma. Although the persistence of predisposing factors such as rhinitis is frequently observed in adults, this has not yet been confirmed in children. AIMS: The aim of this present work is to show the relationship between rhinitis and asthma control in asthmatic children. METHODS: The authors carried out a cross-sectional study by collecting clinical, spirometric, and fractional exhaled nitric oxide (FeNO) data in children aged from 4 to 17 years. RESULTS: One hundred seventeen children were included. Asthma control was optimal in 37.6%, suboptimal in 55.5% and poor in 7.3% of cases. A 74.3% of children were atopic and 62.5% had symptoms 34 of rhinitis. Rhinitis was more frequent when control of asthma was worse (p = .0001). Age (p = .002), asthma control (p < .001), atopy (p = .001), and presence of rhinitis (p = .012) were significantly associated with FeNO. CONCLUSIONS: Our study confirms the strong relationship between upper airways and poor asthma control in the asthmatic child. Symptoms of rhinitis may be partly responsible for the increased fractional exhaled nitric oxide (FeNO) level, independently of the control of asthma. Evaluation of rhinitis should be included to improve assessment of asthma control in children.

Langerhans cell histiocytosis with pulmonary involvement and unilateral pneumothorax.

Langerhans cell histiocytosis (LCH) is a rare disorder of Langerhans cell with unknown etiology, which can uncommonly be associated with pneumothorax. A 14-month-old female is presented here who was referred to our center due to acute respiratory distress. Reticulonodular changes with multiple cystic areas were detected in chest X-ray, whilst extensive honeycombing and cystic changes were seen in high-resolution computed tomography scan. With deterioration of respiratory distress, chest X-ray was repeated, which revealed a unilateral pneumothorax. Meanwhile, some hyperpigmented skin plaques appeared on her skull and back. The biopsy results confirmed the diagnosis of proliferative histiocytosis. Prompt diagnosis of LCH and initiation of appropriate treatment in the patients who present with pneumothorax are vital to prevent further complications and even death in this group of patients.