Pulmonary function of healthy Korean children from three independent birth cohorts: Validation of the Global Lung Function Initiative 2012 equation.

BACKGROUND AND OBJECTIVE: Global Lung Function Initiative (GLI) 2012 equations were developed to resolve the age-related disparity in interpreting spirometry results. Local validation of the equation is needed, especially in Northeast Asian children. This study evaluated the GLI equation in Korean children. METHODS: Spirometry indices (FEV1, FVC, FEV1/FVC, and FEF25%-75%) and clinical information were gathered from three population-based birth cohorts. Predicted GLI reference values and z scores of spirometry results were calculated for 1239 healthy children. The mean, standard deviation of z scores were compared with the expected 0 and 1. Probabilities of falling below the lower limit of normal (LLN) (z score: -1.64) were compared with the expected value 5%. GLI z scores were assessed according to low (<-2), normal (≥-2 and ≤2), and high (>2) BMI z score groups. RESULTS: Mean z scores significantly differed from 0 for FEV1/FVC in males (mean [95% confidence interval]: 0.18 [0.08, 0.27]) and forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) in females (-0.23 [-0.31, -0.15] and -0.26 [-0.36, -0.16], respectively). The standard deviation was larger than 1 for all variables in males and FVC and FEV1/FVC in females. The probability of falling below the LLN was significantly larger than 5% for FEV1 (12.13% [9.64, 14.77]), FVC (15.86% [13.06, 18.81]), and forced expiratory flow at 25%-75% of forced vital capacity (FEF25%-75%) (7.31% [5.29, 9.49]) in males and FVC (11.91% [9.40, 14.60]) in females. FEV1 and FVC z scores increased across low to high body mass index (BMI) groups, and FEV1/FVC decreased from low to high BMI groups. CONCLUSION: GLI equations marginally differ from real-world values, which should be considered by pulmonologists in practice or research.

Association between sensitization and allergic diseases in 7-years-old Korean children.

BACKGROUND: Sensitization is associated with the exacerbation, severity, and prognosis of allergic diseases in children. OBJECTIVE: We characterized the association between sensitization patterns and allergic diseases. METHODS: A cohort of 548 children was enrolled from Panel Study of Korean Children (PSKC) study. Skin prick tests (SPTs) for 18 common allergens, blood tests, and methacholine bronchial challenge tests were performed at age 7. The Korean version of International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire was used. RESULTS: The sensitization rate on SPTs was 46.4%. Sensitization to indoor allergens showed an association with symptoms of asthma (adjusted odds ratio [aOR], 2.39; 95% confidence intervals [95% CIs], 1.10-5.23), allergic rhinitis (AR, aOR 2.08, 95% CIs 1.42-3.06), and atopic dermatitis (AD, aOR 2.36, 95% CIs 1.24-4.50) in the preceding 12 months. In contrast, sensitization to outdoor allergens was associated with AR diagnosis only (aOR 2.40, 95% CIs 1.30-4.41). The number of sensitized allergens was associated with a lifetime diagnosis and symptoms in the preceding 12 months of AR and asthma, but not with AD or BHR. A higher degree of sensitization to indoor allergens was associated with symptoms in the preceding 12 months of asthma, AR, AD, and that for outdoor allergens was associated with symptoms in the prior 12 months of asthma and AR. CONCLUSIONS: The sensitization patterns including allergen type, number, and degree of sensitization are helpful for interpreting the association between sensitization and allergic diseases and identifying the pathophysiologies and diverse phenotypes of allergic diseases.

Pediatric granular cell tumor in the posterior wall of the larynx extending to the trachea.

Granular cell tumor (GCT) is a slow-growing benign neoplasm that can be found in any organ. Pediatric laryngotracheal GCT is rare. We experienced a 6-year-old boy suffering from a barking cough and symptoms of stridor and croup for one month. Head and neck computed tomography revealed a protruding mass that occluded 60% of the airway lumen. Under the impression of hemangioma or papilloma, excision revealed a submucosal non-encapsulated mass. Histologically, the mass was composed of sheets of large polyhedralshaped tumor cells containing plump eosinophilic granular cytoplasm and centrally placed, small, bland-appearing nuclei. The tumor cells were positive for S-100 protein, and voluminous eosinophilic cytoplasm was stained by diastase-resistant periodic acid-Schiff. The present report describes a unique case of a huge pediatric laryngeal GCT extending to the subglottic trachea. We also review the clinical course of pediatric laryngotracheal GCT and emphasize the importance of diagnosing GCT in children.

Vegetable dietary pattern may protect mild and persistent allergic rhinitis phenotype depending on genetic risk in school children.

BACKGROUND: The effect of diet on allergic rhinitis (AR), its severity in children, and whether it modifies AR depending on genetic susceptibility are unknown. We investigated the association between dietary patterns and AR in school children and the influence of diet on AR according to a genetic risk score (GRS). METHODS: Totally, 435 7-year-old school children were recruited from the Panel Study on Korean Children. We used dietary patterns (vegetable, sugar, and meat) and dietary inflammatory index (DII) as dietary parameters. AR and its severity were defined by questionnaires about treatment in the previous 12 months and the Allergic Rhinitis and its Impact on Asthma (ARIA) guideline, respectively. A GRS was calculated using 6 single nucleotide polymorphisms for allergic diseases. RESULTS: A vegetable diet containing a lot of anti-inflammatory nutrients and higher vitamin D level in blood were negatively correlated, while DII was positively correlated with triglyceride level and triglyceride/HDL cholesterol. Vegetable diet (aOR, 95% CI = 0.73, 0.58-0.94) and DII (1.13, 1.01-1.28) were associated with AR risk. In particular, a high-vegetable diet resulted in a lower risk of mild and persistent AR (aOR, 95% CI = 0.24, 0.10-0.56) while a high DII represented a higher risk (2.33, 1.06-5.10). The protective effect of vegetable diet on AR appeared only among children with a lower GRS (adjusted P = .018). CONCLUSIONS: A vegetable dietary pattern characterized by high intake of anti-inflammatory nutrients and higher vitamin D level in blood might be associated with a lower risk of mild and persistent AR. This beneficial effect is modified by a genetic factor.

Risk Factors and Comorbidities Associated With the Allergic Rhinitis Phenotype in Children According to the ARIA Classification.

PURPOSE: Data are lacking on the association between the allergic rhinitis (AR) phenotype and sensitization to specific allergens or bronchial hyperresponsiveness (BHR) in children. We here investigated risk factors and comorbidities, including sensitization to specific allergens and BHR, for the AR phenotype by AR and its Impact on Asthma (ARIA) classification in a general population-based birth cohort study. METHODS: We enrolled 606 children aged 7 years from the Panel Study of Korean Children. The AR phenotype was assigned in accordance with the ARIA classification in children. Skin prick tests and Provocholine provocation test were performed. Risk factors and comorbidities for AR phenotypes were then analyzed. RESULTS: The prevalence of mild and moderate to severe AR in our study cohort was 37.2% and 8.8%, respectively. Recent use of analgesics or antipyretics and current cat ownership were associated with the risk of mild persistent AR. Sensitizations to Dermatophagoides Pteronyssinus (Der p), Japanese hop and cat were associated with moderate to severe persistent AR. Children with moderate to severe AR had a higher risk of current asthma and BHR compared to mild AR cases (adjusted odds ratio [aOR], 5.26; 95% confidence interval [CI], 1.77-15.62). Moderate to severe AR with allergic sensitization was associated with the highest risk of BHR (aOR, 11.77; 95% CI, 3.40-40.74). CONCLUSIONS: Moderate to severe-persistent AR is more closely related to respiratory comorbidities and sensitizations than mild AR. Stratifying the AR phenotype by ARIA classification may assist in disease management.

Profiles and characteristics of bronchial responsiveness in general 7-year-old children.

BACKGROUND: Although bronchial responsiveness (BR) is usually categorized as normal or hyperresponsive to aid the diagnosis of asthma, it exists on a continuous spectrum, not in a dichotomous manner. We aimed to evaluate the distribution profile of BR in a general population of 7-year-olds. METHODS: In 2015, 7-year-old Korean children from a nationwide birth cohort study visited regional study hospitals for skin prick test, standard spirometry, and bronchial provocation to establish reference values for the general population. Their BR degrees were categorized into five ordered groups: hyperresponsive BRs were classified into group 1 (provocative concentration (PC) of methacholine causing a 20% fall in forced expiratory volume in 1 second [FEV1], PC20 of <4 mg/mL) and group 2 (PC20 of ≥4 mg/mL and <16 mg/mL), and nonresponsive BRs were categorized into group 3 (final FEV1 percentage fall after inhaling 16 mg/mL of methacholine [FEV1%fall] of >15% and ≤20%), group 4 (FEV1%fall of >10% and ≤15%), and group 5 (FEV1%fall of ≤10%). RESULTS: In total, 559 subjects finished all tests reliably. Groups 1 and 2 comprised 10.0% and 15.7% of the total population, respectively. Groups 3, 4, and 5 comprised 14.7%, 18.4%, and 41.1%, respectively. As the group number increased, the proportion of those with recent wheezing and those with indoor allergen sensitization decreased (P for trend = 0.001 and P for trend < 0.001, respectively), and the baseline FEV1/FVC increased (P for trend < 0.001) CONCLUSION: BR of the 7-year-olds in the general population, while showing a wide distribution across phenotypes, is associated with allergic symptoms, negatively correlated with baseline lung function and positively correlated with indoor allergen sensitization.

Therapeutic Efficacy and Safety of Prolonged Macrolide, Corticosteroid, Doxycycline, and Levofloxacin against Macrolide-Unresponsive Mycoplasma pneumoniae Pneumonia in Children.

BACKGROUND: We aimed to compare the therapeutic efficacy of prolonged macrolide (PMC), corticosteroids (CST), doxycycline (DXC), and levofloxacin (LFX) against macrolide-unresponsive Mycoplasma pneumoniae (MP) pneumonia in children and to evaluate the safety of the secondary treatment agents. METHODS: We retrospectively analyzed the data of patients with MP pneumonia hospitalized between January 2015 and April 2017. Macrolide-unresponsiveness was clinically defined with a persistent fever of ≥ 38.0°C at ≥ 72 hours after macrolide treatment. The cases were divided into four groups: PMC, CST, DXC, and LFX. We compared the time to defervescence (TTD) after secondary treatment and the TTD after initial macrolide treatment in each group with adjustment using propensity score-matching analysis. RESULTS: Among 1,165 cases of MP pneumonia, 190 (16.3%) were unresponsive to macrolides. The proportion of patients who achieved defervescence within 48 hours in CST, DXC, and LFX groups were 96.9% (31/33), 85.7% (12/14), and 83.3% (5/6), respectively. The TTD after initial macrolide treatment did not differ between PMC and CST groups (5.1 vs. 4.2 days, P = 0.085), PMC and DXC groups (4.9 vs. 5.7 days, P = 0.453), and PMC and LFX groups (4.4 vs. 5.0 days, P = 0.283). No side effects were observed in the CST, DXC, and LFX groups. CONCLUSION: The change to secondary treatment did not show better efficacy compared to PMC in children with macrolide-unresponsive MP pneumonia. Further studies are needed to guide appropriate treatment in children with MP pneumonia.

Prevalence, Risk Factors and Cutoff Values for Bronchial Hyperresponsiveness to Provocholine in 7-Year-Old Children.

BACKGROUND: A US Food and Drug Administration (FDA)-approved drug methacholine chloride (Provocholine®) was recently introduced to Korea where it is now widely used in clinical practice. We aimed to evaluate the prevalence, risk factors and cutoff value of bronchial hyperresponsiveness (BHR) to Provocholine in 7-year-old children. METHODS: Six hundred and thirty-three children from the Panel Study on Korean Children who visited 16 regional hospitals were evaluated. Skin prick tests, spirometry and bronchial provocation tests for Provocholine as well as a detailed history and physical examinations were performed. The bronchial provocation test was reliably performed on 559 of these children. RESULTS: The prevalence of ever-diagnosed asthma via medical records was 7.7%, and that of current asthma (wheezy episode in the last 12 months + diagnosed asthma by physicians) was 3.2%. The prevalence of BHR to Provocholine was 17.2% and 25.8%, respectively, for a PC20 < 8 and < 16 mg/mL. The risk factors for BHR (PC20 < 16 mg/mL) were atopic dermatitis diagnosis and current dog ownership, whereas those for current asthma were allergy rhinitis diagnosis, a history of bronchiolitis before the age of 3, recent use of analgesics/antipyretics and maternal history of asthma. The BHR prevalence trend showed an increase along with the increased immunoglobulin E (IgE) quartile. The cutoff value of PC20 for the diagnosis of current asthma in children at age 7 was 5.8 mg/mL (sensitivity: 47.1%, specificity: 87.4%). CONCLUSIONS: BHR to Provocholine (PC20 < 8 mg/mL) was observed in 17.2% of 7-year-olds children from the general population and the cutoff value of PC20 for the diagnosis of current asthma was 5.8 mg/mL in this age group. The risk factors for BHR and current asthma showed discrepancies suggesting different underlying mechanisms. Bronchial provocation testing with Provocholine will be a useful clinical tool in the future.

Non-Responders to Intravenous Immunoglobulin and Coronary Artery Dilatation in Kawasaki Disease: Predictive Parameters in Korean Children.

BACKGROUND AND OBJECTIVES: In Kawasaki disease (KD), high dose intravenous immunoglobulin (IVIG) significantly lowers the coronary complications. However, some patients either do not respond to initial therapy or develop coronary complications. We aimed to identify the predictive factors for unresponsiveness to initial IVIG therapy and coronary artery dilatation (CAD; defined by Z-score≥2.5) in the acute phase and convalescent phase. SUBJECTS AND METHODS: A retrospective review was conducted of 703 patients with KD, admitted to Gachon University Gil Medical Center between January 2005 and June 2013. The patients were divided into two groups-IVIG responders vs. non-responders-based on the IVIG treatments, and presence of fever after treatment. Further, these groups were divided into two subgroups based on their CAD. RESULTS: Among the 703 patients with KD, the rate of non-responders to initial IVIG was 16.8%. Serum total bilirubin, platelet count, and neutrophil proportion were independent predictive parameters of unresponsiveness (p<0.05). CAD was found in 234 patients (33.3%) in the acute phase, and in 32 patients (4.6%) in the convalescent phase. Male gender, fever duration, serum C-reactive protein, and white blood cell count were related to CAD (p<0.05). CAD was detected more frequently in non-responders than in the responders (47.5% vs. 31.5%, p=0.001). Kobayashi, Egami, and Sano scoring systems applied to our study population reflected low sensitivities (28.0-33.9%). CONCLUSION: Several independent parameters were related to unresponsiveness to the initial IVIG or CAD. These parameters might be helpful in establishing more focused and careful monitoring of high-risk KD patients in Korea.

Hepatitis associated with Mycoplasma pneumoniae infection in Korean children: a prospective study.

PURPOSE: Mycoplasma pneumoniae (MP) infection is a major cause of respiratory infection in school-aged children. Extrapulmonary manifestations of MP infection are common, but liver involvement has been rarely reported. The aim of this study was to determine the clinical characteristics of MP-associated hepatitis. METHODS: This prospective study included 1,044 pediatric patients with MP infection diagnosed serologically with MP IgM at one medical center from January 2006 to December 2012. Eighty of these patients had elevated levels of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT), each greater than 50 IU/L, without any other specific liver disorder and were compared with the 964 children without liver disorders. RESULTS: In total, 7.7% of patients with MP infection had a diagnosis of hepatitis, especially in fall and winter. The ratio of male to female patients was 1.7:1, and the mean age of the patients was 5 years and 5 months. The most common symptoms were cough, fever, and sputum. Anorexia was the most common gastrointestinal symptom, followed by nausea/vomiting, diarrhea, and abdominal pain. Mean levels of AST and ALT were 100.65 IU/L and 118.73 IU/L, respectively. Serum AST/ALT level was normalized within 7.5 days on average without complications. The mean duration of hospitalization (11.3 days) was longer for children with hepatitis than for those without hepatitis (P=0.034). CONCLUSION: MP-associated hepatitis is not uncommon and has a relatively good prognosis. Therefore, clinicians should be concerned about liver involvement in MP infection but avoid further unnecessary evaluation of hepatitis associated with MP.

Successful endovascular treatment of bilateral intralobar pulmonary sequestration with a bridging isthmus in a child.

Pulmonary sequestration refers to aberrant formation of segmental lung tissue that has no connection with the bronchial tree and receives a blood supply from a systemic artery. Bilateral pulmonary sequestration, especially with a bridging isthmus is extremely rare. Although endovascular treatment is regarded as the less invasive alternative for the treatment of pulmonary sequestration, all previously reported bilateral pulmonary sequestrations have been treated surgically. We report the case of a 13-year-old girl who underwent successful endovascular treatment for bilateral pulmonary sequestration with a bridging isthmus. Thoracic CT angiography showed a heterogeneous mass-like consolidation in the both lower lobes connected each other via a bridging isthmus behind the heart. CT also demonstrated an aberrant artery, which originated from the celiac trunk, supplied the sequestration of the left lower lobe, and that a branch from the aberrant artery traversed to the sequestration in the right lower lobe. After percutaneous endovascular embolization using microcoils and gelfoam, the patient had no complications and the bilateral sequestration showed markedly decrease in the size.

Respiratory viruses in neonates hospitalized with acute lower respiratory tract infections.

BACKGROUND: The burden of respiratory syncytial virus (RSV) in neonates has not been clearly studied. The aims of this study were to determine the overall distribution of respiratory viruses in neonates hospitalized with acute lower respiratory tract infectiosns (ALRI) and to describe the clinical characteristics of RSV infections in these neonates. METHODS: From January 2009 through May 2010, neonates aged <1 month who were hospitalized with ALRI and did not have underlying disease were included in the study. Viruses were identified on multiplex reverse transcription polymerase chain reaction using nasal swab samples. Clinical variables were evaluated between the RSV and non-RSV infection groups. RESULTS: Of the 108 infants included in the study, 46 (42.6%) had RSV; human rhinovirus (18.5%), human parainfluenza virus 3 (7.5%), and human metapneumovirus (3.7%) were the next most common infections. Codetections accounted for 8.3% of the cases. Crowding increased the risk of RSV infection compared to the non-RSV group (OR, 16.5; P = 0.001). The RSV group had a greater incidence of dyspnea (P = 0.027), pneumonia (P < 0.001), requirement for oxygen (P < 0.001), and prolonged hospitalization (P = 0.011) than the non-RSV group. CONCLUSIONS: RSV was the most common viral etiology in neonates without underlying diseases who were hospitalized with ALRI. The disease severity of RSV infection was worse than that of other detected viral infections. Strict prevention strategies should be considered in overcrowded situations.

Fractional exhaled nitric oxide and forced expiratory flow between 25% and 75% of vital capacity in children with controlled asthma.

PURPOSE: Fractional exhaled nitric oxide (FeNO) and forced expiratory flow between 25% and 75% of vital capacity (FEF(25-75)) are not included in routine monitoring of asthma control. We observed changes in FeNO level and FEF(25-75) after FeNO-based treatment with inhaled corticosteroid (ICS) in children with controlled asthma (CA). METHODS: We recruited 148 children with asthma (age, 8 to 16 years) who had maintained asthma control and normal forced expiratory volume in the first second (FEV(1)) without control medication for ≥3 months. Patients with FeNO levels >25 ppb were allocated to the ICS-treated (FeNO-based management) or untreated group (guideline-based management). Changes in spirometric values and FeNO levels from baseline were evaluated after 6 weeks. RESULTS: Ninety-three patients had FeNO levels >25 ppb. These patients had lower FEF(25-75)% predicted values than those with FeNO levels ≤25 ppb (P<0.01). After 6 weeks, the geometric mean (GM) FeNO level in the ICS-treated group was 45% lower than the baseline value, and the mean percent increase in FEF(25-75) was 18.% which was greater than that in other spirometric values. There was a negative correlation between percent changes in FEF(25-75) and FeNO (r=-0.368, P=0.001). In contrast, the GM FeNO and spirometric values were not significantly different from the baseline values in the untreated group. CONCLUSION: The anti-inflammatory treatment simultaneously improved the FeNO levels and FEF(25-75) in CA patients when their FeNO levels were >25 ppb.

Utility of fractional exhaled nitric oxide (F(E)NO) measurements in diagnosing asthma.

BACKGROUND: To facilitate the use of fractional exhaled nitric oxide (F(E)NO) as a clinical test, F(E)NO measurements need more clarification. AIM: We sought to evaluate the yield of F(E)NO measurement for the diagnosis of asthma and identify the determinants of F(E)NO in children. METHODS: Two hundred forty five consecutive steroid-naïve patients aged 8-16 years with symptoms suggestive of asthma were included. Children were evaluated using F(E)NO measurements, questionnaires, skin prick tests, spirometries, and methacholine challenge tests. RESULTS: Asthma was diagnosed in 167 children. The sensitivity, specificity, and positive (PPV) and negative predictive values (NPV) of F(E)NO measurements for the diagnosis of asthma at the best cutoff value of 22 ppb were 56.9%, 87.2%, 90.5%, and 48.6%, respectively. At a cutoff value of 42 ppb, specificity and PPV were all 100% but at the cost of very low sensitivity (23.4%) and NPV (37.9%). Both atopy and asthma were identified as independent risk factors associated with high F(E)NO. The association of asthma with high F(E)NO was found only in atopic children because F(E)NO was low in non-atopic children regardless of asthma status. Although highest F(E)NO was observed in atopic asthmatic patients, 28% of these patients had F(E)NO values lower than 22 ppb. CONCLUSION: Atopic asthmatic patients with low F(E)NO values and non-atopic asthmatic patients were responsible for false-negative cases that might contribute to low sensitivity of F(E)NO measurements in diagnosing asthma. High specificity of F(E)NO measurements may help identify patients with atopic asthma among subjects with respiratory symptoms.

Poor adherence and reasons for nonadherence to the asthma guidelines among pediatricians in Korea.

BACKGROUND: Information is limited regarding adherence to the asthma guidelines in Asia, especially for children. OBJECTIVE: The aim of the study was to estimate adherence to the asthma guidelines, and investigate reasons for nonadherence. METHODS: We conducted a cross-sectional questionnaire survey on the primary care pediatricians practicing in Incheon, Korea. RESULTS: Surveys were returned by 81 of 131 eligible primary care pediatricians for a response rate of 61.8%. Almost all respondents (98.8%) had heard of the asthma guidelines, and most (93.8%) had read or received education about them. The classification of asthma severity was well understood with the accuracy of 85.7%. Correct responses for treatments were 51.3% for intermittent, 68.5% for mild persistent and 56.9% for moderate persistent asthma. For severe persistent asthma, the accuracy was high (85.7%). Only 21.5% of the respondents reported routine use of office peak flow measurement for patients with moderate or severe persistent asthma for diagnosis, and fewer (10.3%) used spirometry. A written action plan was reported to be given to only 5.2% of patients with asthma. The principal barrier to adherence was the presence of external barriers (lack of time, equipment, supporting staff etc.). Different barriers were prominent for different types of guideline components. CONCLUSIONS: There is poor adherence to the asthma guidelines in several aspects of their recommendations. Tailored interventions that address the current state of barriers need to be designed and implemented.

Chemotaxis of blood neutrophils from patients with primary ciliary dyskinesia.

Primary ciliary dyskinesia is characterized by chronic upper and lower respiratory infections which are caused by the grossly impaired ciliary transport. Since the cilia and neutrophils both utilize microtubular system for their movement, it has been speculated that neutrophil motility such as chemotaxis might be impaired in patients with primary ciliary dyskinesia. Neutrophils were purified from whole blood from 16 patients with primary ciliary dyskinesia and from 15 healthy controls. Chemotactic responses of neutrophils to leukotriene B(4) (LTB(4)), complement 5a (C5a), and formylmethionylleucylphenylalanine (fMLP) were examined using the under agarose method. The chemotactic differentials in response to LTB4, C5a, and fMLP in neutrophils from the patient group were significantly lower than the corresponding values in neutrophils from the control group (p<0.05 for all comparisons). The difference in chemotactic index between the two groups was statistically significant for LTB4 and fMLP (p<0.05 for both comparisons), but not for C5a (p=0.20). Neutrophils from patients with primary ciliary dyskinesia showed a decreased chemotactic response as compared with those from normal subjects. It is concluded that the increased frequency of respiratory tract infection in patients with primary ciliary dyskinesia is possibly due to the defective directional migration of neutrophils, as well as to the defective mucociliary clearance of the airways.

Improvement in bronchial hyperresponsiveness with inhaled corticosteroids in children with asthma: importance of family history of bronchial hyperresponsiveness.

The extent of improvement in bronchial hyperresponsiveness (BHR) with corticosteroids varies considerably among patients with asthma, although predictive factors for improvement are largely unknown. We tested the hypothesis that the improvement may vary according to family history of BHR. Children with atopic asthma (n = 121) received inhaled budesonide (800 micro g per day) regularly for 6 months. Methacholine provocative concentration causing a 20% fall in FEV(1) was measured before treatment and again after 3 and 6 months of treatment. A methacholine challenge test was also performed in each patient's parents, and the results were analyzed with regard to their children's response to corticosteroid therapy. When the children were classified into large (n = 40) and small (n = 40) improvement groups after 6 months of treatment, the prevalence of BHR and the bronchial responsiveness index were higher in parents of the small improvement group (28.8%, 1.145 +/- 0.104) than in parents of the large improvement group (6.3%, 1.095 +/- 0.064; both, p < 0.01). The magnitude of improvement in BHR at 6 months was lower in children with at least one parent with BHR (n = 45; 1.666 +/- 1.244 doubling doses) than in children with non-BHR parents (n = 76; 2.531 +/- 1.726, p < 0.01). Our results suggest that a family history of BHR may be an important factor in the sensitivity of BHR of individuals with asthma to inhaled corticosteroids.