Comparison of refugee patients with cystic fibrosis and their counterpart children from Turkey during the war.

Since the outbreak of the Syrian civil war in 2011, the population of Arab refugees in Turkey has rapidly increased. While cystic fibrosis (CF) is believed to be rare among Arabs, recent studies suggest it is underdiagnosed. This study aims to present the demographic, clinical, and genetic characteristics of CF patients among Arab refugees in Turkey. Additionally, a comparison is made between the findings in the National CF Registry 2021 in Turkey (NCFRT) and the refugee CF patient group. The study included refugee patients between the ages of 0 and 18 years who were diagnosed with CF and received ongoing care at pediatric pulmonology centers from March 2011 to March 2021. The study examined demographic information, age at diagnosis, age of diagnosis of patients through CF newborn screening (NBS), presenting symptoms, CF transmembrane conductance regulator (CFTR) mutation test results, sputum culture results, weight, height, and body mass index (BMI) z score. Their results were compared with the NCFRT results. The study included 14 pediatric pulmonology centers and 87 patients, consisting of 46 (52.9%) boys and 41 (47.1%) girls. All of the patients were Arab refugees, with 80 (92%) being Syrian. All the patients were diagnosed in Turkey. The median age at diagnosis of patients was 22.33 (interquartile range, 1-258) months. The median age of diagnosis of patients through NBS was 4.2 (interquartile range, 1-12) months. The median age of older patients, who were unable to be included in the NBS program, was 32.3 (interquartile range, 3-258) months. Parental consanguinity was observed in 52 (59.7%) patients. The mutation that was most frequently found was F508del, which accounted for 22.2% of the cases. It was present in 20 patients, constituting 32 out of the total 144 alleles. There was a large number of genetic variations. CFTR genotyping could not be conducted for 12 patients. These patients had high sweat tests, and their genetic mutations could not be determined due to a lack of data. Compared to NCFRT, refugee patients were diagnosed later, and long-term follow-up of refugee CF patients had significantly worse nutritional status and pseudomonas colonization.  Conclusion: Although refugee CF patients have equal access to NBS programs and CF medications as well as Turkish patients, the median age at diagnosis of patients, the median age of diagnosis of patients through NBS, their nutritional status, and Pseudomonas colonization were significantly worse than Turkish patients, which may be related to the difficulties of living in another country and poor living conditions. The high genetic heterogeneity and rare mutations detected in the refugee patient group compared to Turkish patients. Well-programmed NBS programs, thorough genetic studies, and the enhancement of living conditions for refugee patients in the countries they relocate to can have several advantages such as early detection and improved prognosis. What is Known: • Children who have chronic diseases are the group that is most affected by wars. • The outcome gets better with early diagnosis and treatment in patients with Cystic Fibrosis (CF). What is New: • Through the implementation of a newborn screening program, which has never been done in Syria previously, refugee patients, the majority of whom are Syrians were diagnosed with cystic fibrosis within a duration of 4 months. • Despite equal access to the newborn screening program and CF medications for both Turkish patients and refugee patients, the challenges of living in a foreign country have an impact on refugees.

Inflammatory markers in exhaled breath condensate in nonasthmatic children with food allergy.

Allergy is a systemic inflammation; therefore, although the allergic symptom may be seen in a specific organ system, the effects of this inflammation may be seen in other organs. interleukin (IL) IL4, IL5 and IL13 are the major Th2 cytokines and e-cadherin is an epithelial barrier protein. The objective of this research was to assess indicators of inflammation specific to Th2 responses and proteins related to the protective barrier of the airway's inner lining. These assessments were conducted using exhaled breath condensate (EBC), which provides insights into peripheral airway conditions of children suffering from food allergies. The study had 24 patients with food allergy and 24 control individuals younger than three years of age with no history of food reaction. The diagnosis of food allergy was based on food allergen-specific IgE and skin prick test positivity in our clinic and oral food testing in selected cases. EBC samples were obtained by Ecoscreen (Jaegar, Hoechberg, Germany). IL4, IL5, IL13 and E-cadherin levels were measured in these samples by enzyme linked immunoassay. The group of children with food allergies, consisting mainly of 14 girls, had a median age of 16 months, whereas the control group, which included 11 girls, had a median age of 15 months (p= 0.89). Comparing the two groups, children with food allergies exhibited notably lower levels of IL-13 in the EBC compared to the control group (median values of 59.14 and 76.36, respectively,p= 0.02). Conversely, the concentration of IL-4 in the EBC was significantly higher in children with food allergies (median values of 1.94 and 1.29, respectively,p= 0.003). However, the levels of IL-5 and e-cadherin showed no significant differences between the two groups (withp-values of 0.74 and 0.09, respectively) as shown in table1. High level of IL-4 despite the low level of IL-13 in the EBC of children having food allergy may be indicative of an early inflammatory phase that is not yet in the effector phase. Studies about the evolution of this process later in life are needed to assess the role of airway inflammation in children with food allergy who develop asthma.

Patients with cystic fibrosis who could not receive the CFTR modulator treatment: What did they lose in 1 year?

BACKGROUND: Cystic fibrosis (CF) is an autosomal recessive disorder caused by CF transmembrane conductance regulator (CFTR) genetic variants. CFTR modulators improve pulmonary function and reduce respiratory infections in CF. This study investigated the clinical and laboratory follow-up parameters over 1 year in patients with CF who could not receive this treatment. METHODS: This retrospective cohort study included 2018 and 2019 CF patient data from the CF registry of Turkey. Demographic and clinical characteristics of 294 patients were assessed, who had modulator treatment indications in 2018 but could not reach the treatment. RESULTS: In 2019, patients younger than 18 years had significantly lower BMI z-scores than in 2018. During the 1-year follow-up, forced expiratory volumes (FEV1) and FEV1 z-scores a trend toward a decrease. In 2019, chronic Staphylococcus aureus colonization, inhaled antipseudomonal antibiotic use for more than 3 months, oral nutritional supplement requirements, and oxygen support need increased. CONCLUSIONS: Patients who had indications for modulator treatments but were unable to obtain them worsened even after a year of follow-up. This study emphasized the importance of using modulator treatments for patients with CF in our country, as well as in many countries worldwide.

Clinical characteristics of patients requiring lung transplantation referral in national cystic fibrosis registry data.

BACKGROUND: We aimed to determine the number of cystic fibrosis (CF) patients recorded in the Cystic Fibrosis Registry of Türkiye (CFRT) who were in need of lung transplantation (LT) referral and examine clinical differences between patients who were LT candidates due to rapid forced expiratory volume in one second (FEV1) decline and LT candidates without rapid FEV1 decline in the last year to identify a preventable cause in patients with such rapid FEV1 decline. METHODS: All CF patients recorded in the CFRT in 2018 were evaluated in terms of LT. Patients were divided into those with FEV1 below 50% and in need of LT due to a decrease of 20% or more in the previous year (Group 1) and those who did not have FEV1 decline of more than 20% in the previous year but had other indications for LT (Group 2). Demographic and clinical features were compared between the two groups. RESULTS: Of 1488 patients registered in CFRT, 58 had a need for LT. Twenty patients were included in Group 1 and others in Group 2. Our findings did not reveal any significant variations in treatment, chronic infection status, or complications between the two groups. The average weight z-score was significantly higher in Group 1. Positive correlations were detected between weight z-score and FEV1 in 2017 in Group 1 and between FEV1 values in 2017 and 2018 in Group 2. CONCLUSIONS: There appears to be a relationship between the nutritional status and weight z-scores of CF patients and pulmonary function, which may indirectly affect the need for lung transplantation referral.

Pulmonary nodules in children.

Clinicians and radiologist nowadays frequently encounter pulmonary nodules in children, thanks to the widespread use of computed tomography (CT) thorax. Most pulmonary nodules are benign; however, a small number of pulmonary nodules indicate pulmonary malignancy in children, requiring prompt diagnosis and treatment. Incidentally diagnosed pulmonary nodules are common and naturally cause anxiety in families and in clinicians, leading to successive examinations. For this reason, the creation of algorithms for the diagnosis and follow-up of pulmonary nodules, and the definition of advanced imaging requirements will facilitate the management of these patients; early diagnosis and treatment will be provided in patients with malignant tumors, and unnecessary interventions will be minimized in patients with benign nodules. This review is designed to explore current information on nodule definition, diagnostic evaluation, and management in the pediatric age group based on previously obtained data.

The success of the Cystic Fibrosis Registry of Turkey for improvement of patient care.

BACKGROUND: Cystic fibrosis (CF) registries play an essential role in improving disease outcomes of people with CF. This study aimed to evaluate the association of newly established CF registry system in Turkey on follow-up, clinical, growth, treatment, and complications of people with this disease. METHODS: Age at diagnosis, current age, sex, z-scores of weight, height and body mass index (BMI), neonatal screening results, pulmonary function tests, history of meconium ileus, medications, presence of microorganisms, and follow-up were evaluated and compared to data of people with CF represented in both 2017 and 2019 registry data. RESULTS: There were 1170 people with CF in 2017 and 1637 in 2019 CF registry. Eight hundred and fourteen people were registered in both 2017 and 2019 of whom z-scores of heights and BMI were significantly higher in 2019 (p = 0.002, p =0.039, respectively). Inhaled hypertonic saline, bronchodilator, and azithromycin usages were significantly higher in 2019 (p =0.001, p = 0.001, p = 0.003, respectively). The percent predicted of forced expiratory volume in 1 sec and forced vital capacity were similar in 2017 and 2019 (88% and 89.5%, p = 0.248 and 84.5% and 87%, p =0.332, respectively). Liver diseases and osteoporosis were significantly higher, and pseudo-Bartter syndrome (PBS) was significantly lower in 2019 (p = 0.011, p = 0.001, p = 0.001, respectively). CONCLUSIONS: The z-scores of height and BMI were higher, the use of medications that protect and improve lung functions was higher and incidence of PBS was lower in 2019. It was predicted that registry system increased the care of people with CF regarding their follow-up. The widespread use of national CF registry system across the country may be beneficial for the follow-up of people with CF.

Adipocyte related peptides - galanin and resistin in endometrioid type endometrium cancer.

OBJECTIVES: The aim of (this) study was to investigate concentrations of galanin and resistin in patients with endometrioid type endometrium cancer. MATERIAL AND METHODS: A total of 85 patients (52 Endometrioid type Endometrium Cancer patients and 33 healthy controls) were included in the study. Serum galanin and resistin levels were measured by an enzyme-linked immunosorbent assay (ELISA). RESULTS: It was found that the sensitivity and specificity of galanin at the cut off level of 0,37 ng/mL, was 82.96% and 68.78% respectively (AUC = 0.795, CI:0.691-0.898, p < 0.001). Sensitivity and specificity of resistin at the 0.27 ng/mL cut off level, was found to be 82.95% and 59.12% respectively (AUC = 0.705, CI:0.588-0.822, p < 0.001) for prediction of endometrioid type endometrium cancer diagnosis. Bivariate logistic regression analysis showed that, increased galanin concentration, greater than 0.37 ng/mL, increased the risk of having endometrioid type endometrium cancer 10.2 times (95% CI: 3.425-30.881, p < 0.001) and resistin concentration > 0.27 ng/mL, increased the risk of having endometrioid type endometrium cancer 5.6 fold (95% CI: 1.939-16.282, p = 0.001). On the other hand, according to adjusted Odds Ratio results of the multiple logistic regression analysis, effect of interaction between galanin and resistin on having endometrioid type endometrium cancer was statistically significant. Increased galanin concentration > 0.37 ng/mL with increased resistin concentration > 0.27 ng/mL had adjusted Odds Ratio = 27.182 times greater risk of having endometrioid type endometrium cancer (95% CI: 6.653 to 111.109, p < 0.001). CONCLUSIONS: Increased galanin and resistin levels, either separately or together with, seemed to increase the risk of endometrioid type endometrium cancer other than different risk factors.

Clinical findings of patients with cystic fibrosis according to newborn screening results.

BACKGROUND: Cystic fibrosis (CF) is a lethal recessive genetic disease caused by loss of function associated with mutations in the CF trans-membrane conductance regulator. It is highly prevalent (approximately 1 in 3,500) in Caucasians. The aim of this study was to compare demographic and clinical features, diagnostic tests, treatments, and complications of patients with CF whose newborn screening (NBS) with twice-repeated immune reactive trypsinogen testing was positive, normal, and not performed. METHODS: In this study, 359 of all 1,488 CF patients recorded in the CF Registry of Turkey in 2018, who had been born through the process of NBS, were evaluated. Demographic and clinical features were compared in patients diagnosed with positive NBS (Group 1), normal (Group 2), or without NBS (Group 3). RESULTS: In Group 1, there were 299 patients, in Group 2, there were 40 patients, and in Group 3, there were 20 patients. Among all patients, the median age at diagnosis was 0.17 years. The median age at diagnosis was higher in Groups 2 and 3 than in Group 1 (P = 0.001). Fecal elastase results were higher in Group 2 (P = 0.033). The weight z-score was lower and chronic Staphylococcus aureus infection was more common in Group 3 (P = 0.017, P = 0.004, respectively). CONCLUSIONS: Frequency of growth retardation and chronic S. aureus infection can be reduced with an early diagnosis using NBS. In the presence of clinical suspicion in patients with normal NBS, further analyses such as genetic testing should be performed, especially to prevent missing patients with severe mutations.

Destiny of airway disease: interplay between epithelial barrier and the innate immune system.

When the organism encounters a foreign substance, it responds with mutual and regular interactions at different stages of the immune system. In airway diseases, the first encounter is at the epithelial level, where innate immune cells and their responses form the first leg of the protective mechanism. The most important barrier for environmental damage is the epithelial barrier. However, the epithelial barrier is not just a mechanical barrier. The formation of the microbiome on the epithelium and the tolerance or intolerance to environmental factors are vital. This vital balance is maintained between the epithelial surface and the subepithelial innate immune system. This is achieved by the epithelial line, which is a mechanical and functional barrier between them. In this respect, epithelial barrier function preservation has an important role in the development and prognosis of airway disease.

May the first-line treatment for foreign body aspiration in childhood be flexible bronchoscopy?

INTRODUCTION: Rigid bronchoscopy (RB) is the traditional treatment in foreign body (FB) aspiration in childhood but is a traumatic and invasive procedure. However, flexible optic bronchoscopy (FoB) is a noninvasive and nontraumatic respiratory intervention. The aim of this study was to evaluate FoB as a first-line treatment modality in pediatric cases presenting with a preliminary diagnosis of FB aspiration. METHODS: Subjects who underwent FoB under general anesthesia with the preliminary diagnosis of FB aspiration were enrolled in this cross-sectional study. Two cases were inherited from pediatric surgery because they were not removed with FoB. The demographic, clinical, and radiological findings at the presentation were recorded. Results of success rate and complications were recorded. RESULTS: Among the FB aspiration cases age range of 7 months to 16 years. FoB demonstrated a FB in the airways of 31 (62.2%) subjects. The duration of the symptoms in the subjects was 9.1 ± 8.8 days. Three of the cases were taken over from pediatric surgery because they were not removed with RB. Most commonly encountered FB's were organic materials (n = 20, 64%). FoB was successful in removing the FB from the proximal and also distal airways in 93% of the subjects. No significant complications and side effects were observed except post-FoB cough. CONCLUSION: This result has shown that FoB for the treatment of FB aspiration is successful in removing FB aspiration from both the proximal and distal airway that the RB cannot remove. Furthermore, FoB did not have any significant airway complication. FoB may be used as the first-line treatment modality for FB aspiration instead of RB in childhood the fact that noninvasive and nontraumatic respiratory intervention.

E-Cadherin: An Important Functional Molecule at Respiratory Barrier Between Defence and Dysfunction.

While breathing, many microorganisms, harmful environmental particles, allergens, and environmental pollutants enter the human airways. The human respiratory tract is lined with epithelial cells that act as a functional barrier to these harmful factors and provide homeostasis between external and internal environment. Intercellular epithelial junctional proteins play a role in the formation of the barrier. E-cadherin is a calcium-dependent adhesion molecule and one of the most important molecules involved in intercellular epithelial barier formation. E-cadherin is not only physical barrier element but also regulates cell proliferation, differentiation and the immune response to environmental noxious agents through various transcription factors. In this study, we aimed to review the role of E-cadherin in the formation of airway epithelial barier, its status as a result of exposure to various environmental triggers, and respiratory diseases associated with its dysfunction. Moreover, the situations in which its abnormal activation can be noxious would be discussed.

Food-induced anaphylaxis in early childhood and factors associated with its severity.

Background: Several factors that increase the risk of severe food-induced anaphylaxis have been identified. Objective: We aimed to determine the demographic, etiologic, and clinical features of food-induced anaphylaxis in early childhood and also any other factors associated with severe anaphylaxis. Methods: We carried out a medical chart review of anaphylaxis cases from 16 pediatric allergy and immunology centers in Turkey. Results: The data of 227 patients with 266 food-induced anaphylaxis episodes were included in the study. The median (interquartile range) age of the first anaphylaxis episode was 9 months (6-18 months); 160 of these patients were boys (70.5%). The anaphylaxis episodes were mild in 75 cases (28.2%), moderate in 154 cases (57.9%), and severe in 37 cases (13.9%). The most frequent food allergens involved were cow's milk (47.4%), nuts (16.7%), and hen's egg (15.8%). Epinephrine was administered in only 98 (36.8%) of these anaphylaxis episodes. A logistic regression analysis revealed two statistically significant factors that were independently associated with severe anaphylaxis: the presence of angioedema and hoarseness during the anaphylactic episode. Urticaria was observed less frequently in patients who developed hypotension. In addition, confusion and syncope were associated with 25.9- and 44.6-fold increases, respectively, in the risk of concomitant hypotension. Conclusion: Cow's milk, nuts, and hen's egg caused the majority of mild and moderate-to-severe anaphylaxis episodes. The presence of angioedema and hoarseness in any patient who presents with a history of food-induced anaphylaxis should alert clinicians that the reaction may be severe. In addition, the presence of confusion, syncope, or stridor probably indicates concomitant hypotension.

Two different methods of lidocaine inhalation before diagnostic flexible bronchoscopy: effects on post-bronchoscopy respiratory symptoms

Background/aim: Use of topical anesthesia before flexible bronchoscopy for the evaluation of the upper airways prevents cough and stridor during and after the procedure while reducing the need for sedation. In practice, lidocaine is the medication of choice before bronchoscopy. There various types of nebulizers used for inhalation treatments. In this study, we compared the respiratory tract symptoms after flexible bronchoscopy between children who received pre-procedure topical lidocaine with mesh or jet nebulizers. Materials and methods: We enrolled 4­18 years old subjects that underwent flexible bronchoscopy due to treatment-resistant asthma in this retrospective case-control study. Twenty subjects received topical lidocaine with jet nebulizers while 20 received it with mesh nebulizers. Age, sex, duration of bronchoscopy, duration of anesthesia, time to awaken, and time to recovery were recorded as well as cough and laryngospasm scores after flexible bronchoscopy. Results: Severe cough after flexible bronchoscopy was not encountered in the mesh nebulizers group but was seen in 10% of the jet nebulizers group (p = 0.027). On the other hand, age, sex, duration of bronchoscopy, duration of anesthesia, time to awaken, and time to recovery were not significantly different between the mesh and jet nebulizer groups (p = 0.44, 0.34, 0.51, 0.88, 0.88, and 0.22, respectively). Moreover, croup and laryngospasm scores between the two groups were similar (p = 0.62, 0.50 respectively). Cough score was significantly worse jet nebulizers group (p = 0.03). Conclusion: Topical lidocaine application with mesh nebulizers decreases the most common complication, cough, after flexible bronchoscopy in children more effectively compare to jet nebulizers. Thus, mesh nebulizers may be a faster way of nebulization before flexible bronchoscopy as an alternative to jet nebulizers.

Measurement of Airway Epithelial Permeability: Methods and Protocols.

The epithelial barrier is the basic unit that ensures the continuation of life for all living things. It provides separation of living cells or organelles from nature and microenvironment. Thus, life and functions continue. It is the same for the human organism. However, the normal properties of this epithelial barrier may differ in each organ and tissue. The two most important barriers that separate humans from nature and their microenvironment are the respiratory tract and the gastrointestinal system. The respiratory tract continues from the tip of the nose to the alveola. The epithelial barrier in the respiratory tract has to be semipermeable in places. However, the increase in permeability exceeding the limit is the cause of the diseases and the increase in clinical weight. Therefore, measuring the level of epithelial permeability in these units is important for understanding experimental models, disease cause, clinical severity, and prognosis. In this article, the measurement of epithelial permeability in the respiratory tract will be discussed with in vitro, in vivo aspects and methods.

Anti-VEGF treatment suppresses remodeling factors and restores epithelial barrier function through the E-cadherin/ß-catenin signaling axis in experimental asthma models.

Besides maintaining a physical barrier with adherens junctional (AJ) and tight junctional proteins, airway epithelial cells have important roles in modulating the inflammatory processes of allergic asthma. E-cadherin and ß-catenin are the key AJ proteins that are involved in airway remodeling. Various mediators such as transforming growth factor-ß (TGF-ß), epidermal growth factor (EGF), fibroblast growth factor (FGF), platelet derived growth factor (PDGF), insulin-like growth factor (IGF), tumor necrosis factor-α (TNF-α) and angiogenic factors, such as vascular endothelial growth factor (VEGF), are released by the airway epithelium in allergic asthma. The signaling pathways activated by these growth factors trigger epithelial-mesenchymal transition (EMT), which contributes to fibrosis and subsequent downregulation of E-cadherin. The present study used a mouse asthma model to investigate the effects of anti-VEGF, anti-TNF and corticosteroid therapies on growth factor and E-cadherin/ß-catenin expression. The study used 38 male BALB/c mice, divided into 5 groups. A chronic mouse asthma model was created by treating 4 of the groups with inhaled and intraperitoneal ovalbumin (n= 8 per group). Saline, anti-TNF-α (etanercept), anti-VEGF (bevacizumab) or a corticosteroid (dexamethasone) were applied to each group by intraperitoneal injection. No medication was administered to the control group (n=6). Immunohistochemistry for E-cadherin, ß-catenin and growth factors was performed on lung tissues and protein expression levels assessed using H-scores. Statistically significant differences were observed in E-cadherin, ß-catenin, EGF, FG, and PFGF (P<0.001 for all) as well as the IGF H-scores between the five groups (P<0.005). Only anti-VEGF treatment caused E-cadherin and ß-catenin levels to increase to the level of non-asthmatic control groups (P>0.005). All treatment groups had reduced TGF-ß, PDGF and FGF H-scores in comparison with the untreated asthma group (P=0.001). The EGF and IGF levels were not significantly different between the untreated asthmatic and non-asthmatic controls. The results suggested that anti-VEGF and TNF-α inhibition treatments are effective in decreasing growth factors, in a similar manner to conventional corticosteroid treatments. Anti-VEGF and TNF inhibition therapy may be an effective treatment for remodeling in asthma while offering an alternative therapeutic option to steroid protective agents. The data suggested that anti-VEGF treatment offered greater restoration of the epithelial barrier than both anti-TNF-α and corticosteroid treatment.

Gynecologic manifestations in Emberger syndrome.

Immune system vulnerability seems to play a significant role in the development and malignant transformation of pre-malignant squamous cell lesions. Emberger syndrome is a condition that affects the immune system, which is caused by GATA2 gene mutations. Our objective was to present the gynecologic expressions of this rare syndrome in our case. Here, we discussed a relatively young patient with findings related to Emberger syndrome such as recurrent infections, myelodysplastic syndrome, lower extremity edema, and multifocal, multicentric premalignant/malignant genital lesions. Sequencing of the GATA2 gene was accomplished for suspected Emberger syndrome and a point mutation in intron5, c1143+8C >T was detected. Gynecologists may play an important role in the early detection of Emberger syndrome and guiding multidisciplinary treatment options as the initial signs related to this rare entity can appear on the genitalia.

Maternal psychiatric status and infant wheezing: The role of maternal hormones and cord blood cytokines.

RATIONALE: Maternal psychosocial stress might be associated with development of allergic diseases in the offspring. OBJECTIVES: To evaluate the association of maternal depression and anxiety with ever wheezing and recurrent wheezing among infants and to assess the role of maternal hypothalamo-pituatary-adrenal axis changes and fetal immune response in this association. METHODS: This study encompasses two designs; cohort design was developed to evaluate the association of prenatal depression with development of wheezing in infants while nested case-control design was used to assess the role of maternal cortisol and tetranectin and cord blood interleukin 13 and interferon γ. RESULTS: We enrolled 697 pregnant women. Elementary school graduate mother (odds ratio [OR] = 1.5, p = .06), maternal smoking during pregnancy (OR = 3.4, p = .001), familial history of asthma (OR = 2.7, p < .001) increased the risk of ever wheezing. Elementary school graduate mother (OR = 2.6, p = .002), maternal smoking during pregnancy (OR = 4.8, p < .001) and familial history of asthma (OR = 1.7, p = .01) increased the risk of recurrent wheezing. Maternal previous psychiatric disease, or Edinburgh Postnatal Depression Scale or Spielberger State-Trait Anxiety Inventory scores were not associated with wheezing. Maternal tetranectin levels were significantly higher among never wheezers compared to the ever wheezers (264.3 ± 274.8 vs. 201.6 ± 299.7, p = .04). CONCLUSIONS: In conclusion, the major risk factors for ever wheezing and recurrent wheezing were maternal smoking, level of education and family history of asthma. However, maternal depression and anxiety were not determined as risk factors for wheezing. Maternal tetranectin carries potential as a biomarker for wheezing in the infant.

Fetal Programming: Lung Health and Disease.

Fetal programming is a mechanism whereby stimuli acting on the developing fetus influence the development of the fetus in a way that may set the stage for adult health and disease. These stimuli may be environmental, such as maternal smoking; metabolic, such as the maternal diet and nutrition; or endocrine, such as diabetes or stress, and may extend over several generations. The endocrine system influences fetal programming with effects of insulin, thyroid hormones, and glucocorticoid hormones. Epigenetic information may be modified by DNA methylation, histone modifications, and micro RNAs due to environmental exposures. In this review, we describe the normal development of the lungs and the major factors that may influence lung growth and development with the potential for sequelae into adult life.