The Usefulness of a Transbronchial Lung Cryobiopsy for Diffuse Bronchiolitis

We herein report four cases of diffuse bronchiolitis proven by a transbronchial lung cryobiopsy (TBLC). Based on various aspects, including the pathological findings, we definitively diagnosed two patients with diffuse panbronchiolitis (DPB) and the other two with primary ciliary dyskinesia (PCD). One of the DPB patients had more severe peribronchiolar fibrosis than the other, and the disease course was refractory to macrolide therapy. One of the PCD patients was additionally diagnosed with combined constrictive bronchiolitis. This report highlights the importance of a TBLC in the differentiation of bronchiolitis, suggesting its utility for helping pulmonologists formulate a treatment strategy.     

Diffuse panbronchiolitis as a pulmonary complication in patients with adult T-cell leukemia

Forty-three cases of adult T-cell leukemia (ATL) admitted to our hospital between 1982 and 1987 were studied. Three of those were found to be complicated with diffuse panbronchiolitis (DPB). The incidence of DPB is considered to be significantly higher in patients with ATL. The three DPB-complicated cases composed one case each of the smoldering, chronic, and acute type of ATL. In each type, DPB preceded overt ATL and Candida albicans was found in sputa following detection for bacteria. The DPB complication apparently worsened the prognosis of the ATL patients. We have discussed a possible relationship between ATL and DPB.     

Risk Factors for Montelukast Treatment Failure in Step-Down Therapy for Controlled Asthma

Background. Leukotriene receptor antagonists including montelukast are an option for step-down therapy for mild asthmatics controlled on low-dose inhaled corticosteroids (ICS). Because some patients fail montelukast step-down therapy, it would be helpful for clinicians to be able to predict the risk of treatment failure. Objectives. To determine patient characteristics associated with montelukast treatment failure and develop a clinical index to predict the risk of montelukast treatment failure. Methods. Using the 165 participants in the Leukotriene or Corticosteroid or Corticosteroid-Salmeterol Study (LOCCS) trial who were stepped down from low-dose ICS to montelukast, we determined associations between enrollment variables and treatment failure. We constructed a montelukast failure index to predict the risk of montelukast treatment failure during step-down. To assess its specificity for montelukast, index performance was evaluated in the other LOCCS treatment groups. Results. Characteristics independently associated with montelukast treatment failure included age of asthma onset <10 years old (OR = 2.39; 95% CI = 1.17–5.02; p = .018), need for steroid burst in the last year (OR = 2.39; 95% CI = 1.13–5.09; p = .022), and pre-bronchodilator forced expiratory volume in 1 s (FEV₁) (OR = 1.44 per 10% lower % predicted; 95% CI = 1.07–1.97; p = .016). A montelukast failure index was generated from these three variables (range: ?5 to 7 points). Scores <0 predicted low risk (<0.20) of treatment failure, whereas scores >5 predicted high risk (>0.60) of treatment failure. Conclusion. Early asthma onset, worse asthma control in the last year, and lower pre-bronchodilator FEV₁ are associated with montelukast treatment failure. A montelukast failure index is proposed to quantify the risk of failure prior to treatment initiation.     

Effects of Stress in Early Life on Immune Functions in Rats With Asthma and the Effects of Music Therapy

Objective. Although studies have shown that psychological stress has detrimental effects on bronchial asthma, there are few objective data on whether early-life stress, as early postnatal psychosocial environment, has a long-lasting effect on adult asthma and the potential pathophysiologic mechanism. This study aims to examine the effects on immune function and hypothalamic-pituitary-adrenal (HPA) axis responses in adult asthmatic rats that experienced stress in early life and the potential ameliorative effects of music therapy on these parameters. Methods. Forty male Wistar rat pups were randomly assigned to the asthma group, the adulthood-stressed asthma group, the childhood-stressed asthma group, the music group, and the control group. Restraint stress and Mozart's Sonata K.448 were applied to ovalbumin (OVA)-induced asthmatic rats to establish psychological stress and music therapy models. The levels of serum corticosterone were examined in both childhood after stress and adulthood after OVA challenge. Immune indicators in blood, lung, and brain tissues were measured after the last OVA challenge. Results. Stress in both childhood and adulthood resulted in increases in leukocyte and eosinophil numbers and serum interleukin (IL)-4 levels. The adulthood-stressed group demonstrated increased corticosterone levels after challenge, whereas the childhood-stressed group showed increased corticosterone concentration in childhood but decreased level in adulthood. Central IL-1β exhibited a similar tendency. Music group rats showed reduced serum IL-4 and corticosterone. Conclusions. Stress in childhood and adulthood resulted in different HPA axis responsiveness in the exacerbation of markers of asthma. These data provide the first evidence of the long-term normalizing effects of music on asthmatic rats.     

Biochemical Markers as a Response Guide for Steroid Therapy in Asthma

Background. Exhaled breath condensate pH and hydrogen peroxide concentration is a non-invasive, simple and inexpensive assay that can be performed for monitoring in patients with asthma. Objective. To evaluate the possibility of usefulness of expired breath condensate pH and H₂O₂ concentration as well as serum total antioxidant capacity and malondialdehyde as markers for steroid treatment response. Patients and methods. A total of 153 patients were included in this study (age range 18 to 64 years). Asthmatic patients, regularly followed for at least 3 months, were randomly recruited for the study over a period of one month. All patients received inhaled beclomethasone dipropionate (1,000 μ g daily in four divided doses) and salbutamol inhalers (800 μ g daily in four divided doses) for 4 weeks. Expired breath condensate was collected at the end of the study to determine hydrogen peroxide concentration and pH. Venous blood samples were collected for determination of total antioxidant capacity and malondialdehyde as markers of peroxidation. Results. In asthmatic patients with poorly controlled asthma, expired breath condensate hydrogen peroxide concentration was higher and the pH was lower than stable asthma. Serum malondialdehyde concentration in poorly controlled asthma was higher (6.98 μ mol/L), and total antioxidant capacity was lower (589 μ mol/L) than in stable asthma. Conclusion. Exhaled hydrogen peroxide concentration and pH can be used as predictors for monitoring of nonresponse to asthma treatment.     

An Observational Investigation of Dysfunctional Breathing and Breathing Control Therapy in a Problem Asthma Clinic

Objectives. Dysfunctional breathing (DB) is recognized as an associated problem in patients with asthma and may be identified by the Nijmegen questionnaire. We conducted an observational study to determine if breathing control therapy (BCT) improved Nijmegen scores or asthma-related quality of life in patients attending a problem asthma clinic. Methods. Nijmegen and Mini Asthma Quality of Life (Mini-AQLQ) questionnaires were completed. Patients with a positive Nijmegen (≥ 23, DB) were referred for BCT and progressive exercise testing (PET) to seek confirmation of dysfunctional breathing. Follow-up questionnaire data were collected at 6 months. Results. A total of 102 patients were studied. The total mean Nijmegen score was 26.4 (range 1–61). Those with a score ≥ 23 (DB group, n = 65, 64%) had significantly lower Mini-AQLQ (mean 2.83) than the non-DB group (n = 37, mean 4.12, 95% CI for difference 0.87, 1.87, p < 0.0001). There was a strong relationship between Nijmegen score and Mini-AQLQ (r = ?0.63, p < 0.001) at baseline; 10 of 17 DB patients who completed PET showed inappropriate hyperventilation. Follow-up data, available for Nijmegen and Mini-AQLQ in 44 and 46 patients respectively, showed no significant change in either of these parameters. Conclusions. The strong relationship between Mini-AQLQ and Nijmegen scores and poor relationship between Nijmegen scores and PET-identified inappropriate hyperventilation suggest that a positive Nijmegen score overestimates the presence of dysfunctional breathing in patients with moderate to severe asthma. We found no evidence that a moderate intensity breathing control intervention had any impact on Nijmegen scores or asthma-related quality of life in this patient group.     

Percutaneous Left Atrial Appendage Closure in a Patient with Diffuse Alveolar Hemorrhaging Associated with Anticoagulant Therapy and Atrial Fibrillation

Diffuse alveolar hemorrhaging (DAH) due to oral anticoagulation (OAC) is a life-threatening condition that leads to severe respiratory failure. There is a clinical dilemma in that OAC-induced DAH often forces the discontinuation of OAC therapy and the administration of high-dose corticosteroids, which increases the risk of stroke and cardiovascular events. We herein report the first case of OAC-induced DAH and atrial fibrillation (AF) in a patient who completely discontinued OAC therapy and high-dose corticosteroids after experiencing percutaneous left atrial appendage (LAA) occlusion. This case suggests that percutaneous LAA closure may aid in the management of OAC-induced DAH and AF.     

Prognosis of Adult Asthma After Normalization of Bronchial Hyperresponsiveness by Inhaled Corticosteroid Therapy

Background: Inhaled corticosteroids (ICSs) are the most effective anti-inflammatory drugs for adult asthma and can improve not only clinical symptoms but also bronchial hyperresponsiveness (BHR). However, the prognosis of adult asthma has not been well studied, and it remains to be elucidated precisely how long treatment with ICSs should be continued once clinical remission is achieved. Objectives: We examined whether ICS use could be withdrawn or reduced without exacerbation of disease. Methods: We retrospectively studied 374 adult patients with asthma to determine which factors predicted the elimination or reduction of ICS treatment without exacerbations of disease after the achievement of normalized BHR to acetylcholine. The patients were classified into three groups: Group 1 had symptoms within 6 months of normalization and needed to continue therapy; group 2 received the equivalent of ≥ 400 μ g fluticasone propionate until BHR normalization, did not have symptoms in the 6 months after normalization, and then had their doses of ICSs halved; and group 3 received the equivalent of ≤ 200 μ g fluticasone propionate at an enrollment, did not have symptoms in the 6 months after normalization, and then had all ICSs withdrawn. The primary outcome measure was the presence of clinical symptoms. We used multiple logistic regression and a Kaplan-Meier analysis to analyze the factors predicting remission. Results: Twenty-nine patients in group 3 remained asymptomatic for more than 30 months (mean 47.1 ± 12.4 months) after discontinuing ICS therapy. The predictive markers of remission were low levels of eosinophils in the sputum, high %V₅₀ at the first hospital visit, and the need for only a low daily dose of ICS to induce normalized BHR. Conversely, patients with severe BHR at the first hospital visit, low %FEV₁ at normalized BHR, and a need for high-dose ICSs to reach normalized BHR could not reduce or discontinue treatments. Conclusion: Some adult patients with asthma whose BHR is normalized by ICS therapy can achieve remission from disease exacerbation after discontinuation of ICSs. However, patients with severe asthma or asthma of long duration may not achieve remission even if their BHR is normalized.     

Asthma Remission in a Patient with Rheumatoid Arthritits While on Antiangiogenesis Therapy During a Rheumatoid Arthritis Trial Demonstrated by Forced Oscillation and Spirometry

Asthma is a chronic inflammatory condition. An integral part of the inflammation is angiogenesis (neovascularization). This report describes a patient with rheumatoid arthritis (RA) and moderately severe asthma despite maintenance on inhaled corticosteroids (ics) and intermittent systemic steroids (ss). While enrolled in a clinical trial for RA employing MEDI-522 (Vitaxin), her asthma symptoms remitted substantially, with significant improvement in spirometry and airflow resistance measured by forced oscillation. The patient was able to discontinue ics and required no ss while taking MEDI-522. After termination of the clinical trial, the patient's asthma symptoms again increased and required reinstitution of ics for control.     

Asthma Remission in a Patient with Rheumatoid Arthritits While on Antiangiogenesis Therapy During a Rheumatoid Arthritis Trial Demonstrated by Forced Oscillation and Spirometry

Asthma is a chronic inflammatory condition. An integral part of the inflammation is angiogenesis (neovascularization). This report describes a patient with rheumatoid arthritis (RA) and moderately severe asthma despite maintenance on inhaled corticosteroids (ics) and intermittent systemic steroids (ss). While enrolled in a clinical trial for RA employing MEDI-522 (Vitaxin), her asthma symptoms remitted substantially, with significant improvement in spirometry and airflow resistance measured by forced oscillation. The patient was able to discontinue ics and required no ss while taking MEDI-522. After termination of the clinical trial, the patient's asthma symptoms again increased and required reinstitution of ics for control.     

Development and Preliminary Validation of the Asthma Intensity Manifestations Score (AIMS) Derived from Asthma Control Test,FEV1, Fractional Exhaled Nitric Oxide,and Step Therapy Assessments

Objective. Inherent asthma severity is difficult to assess clinically. The purpose of this study was to develop an Asthma Intensity Manifestations Score (AIMS) as a surrogate for asthma severity. Methods. Three hundred and four patients treated with inhaled corticosteroids completed the Asthma Control Test (ACT), underwent spirometry, and fractional exhaled nitric oxide (FENO) testing, and reported their current medications. These parameters (defined as ACT < 16, forced expiratory volume in 1 second [FEV₁] < 80% predicted, FENO > 50 ppb, and Expert Panel Report [EPR3] step care level >3) were related to prior year outcomes to develop the AIMS and to follow-up year outcomes to validate it. Results. FENO was independently related to prior year short-acting beta agonist (SABA) ≥ 7 (odds ratio [OR] 2.9); ACT (OR 4.9), FEV₁ (OR 3.3), and step care (OR 3.9) were independently related to prior year systemic corticosteroid (SCS) ≥ 2. Thus, all the four items were chosen for the AIMS (0–4 points). AIMSs were linearly related to follow-up year SABA ≥ 7, any SCS, SCS ≥ 2, and emergency hospital care (all p < .01). Compared to patients with AIMSs <2, patients with AIMSs ≥2 were at more than a fourfold greater risk of requiring ≥2 SCS in the following year and were at a 2–2.8-fold greater risk of experiencing other adverse outcomes during that time period. Conclusions. The AIMS is linearly related to future year adverse asthma outcomes. Further studies will be necessary to confirm its utility as a surrogate for asthma severity in clinical practice and clinical research.     

Long Term Oral Anticoagulant Therapy With Warfarin: Experience With Local Patient Population in Kuwait

Warfarin (Coumadin) continues to remain the mainstay of oral anticoagulant therapy (OACT) for thromboprophylaxis for both venous thromboembolic disease (VTD) and cardiac indications. However it needs careful monitoring because of its narrow window of target activity level, interaction with numerous medications and food items, caution for use in patients with co-morbidities like hepatic and renal impairment and bleeding lesions and the risk of major hemorrhage. A large part of its success and safety requires the patients own understanding and participation in its control. In a retrospective study on 153 patients on long term OACT with warfarin, we have analyzed the influence of various personal characteristics of the local patient population like age, gender, nationality, education and financial status, family size, family style, manner of drug administration and number of other medications prescribed for co-morbidities. Ability to achieve consistently efficacious target level of anti coagulant activity is adversely affected by older age, female gender, lower education status, larger family size, joint family setting, dependence on domestic servants to administer warfarin and larger number of other medications taken for co-morbidities. Thirty-seven patients were identified from such vulnerable personal characteristics and assigned to a separate anticoagulant therapy control clinic with specific arrangements for stricter control. This group of patients was studied prospectively for 18 months. Significant improvement was apparent on comparison of their performance before and after assignment to the separate clinic.     

Improving Care for Urban Children with Asthma: Design and Methods of the School-Based Asthma Therapy (SBAT) Trial

The School Based Asthma Therapy (SBAT) trial builds on a pilot study in which we found that school-based administration of preventive asthma medications for inner-city children reduced asthma symptoms. However, the beneficial effects of this program were seen only among children not exposed to environmental tobacco smoke (ETS). The current study is designed to establish whether this intervention can be enhanced by more stringent adherence to asthma guidelines through the addition of symptom-based medication dose adjustments, and whether smoke-exposed children benefit from the intervention when it is combined with an ETS reduction program. The intervention consists of both administration of preventive asthma medications in school (with dose adjustments according to NHLBI guidelines) and a home-based ETS reduction program utilizing motivational interviewing principles. This paper describes the methodology, conceptual framework, and lessons learned from the SBAT trial. Results of this study will help to determine whether this type of comprehensive school-based program can serve as a model to improve care for urban children and reduce disparities.