Intractable Asthma Research Articles

Therapeutic Potential for Intractable Asthma by Targeting L-Type Amino Acid Transporter 1.

Bronchial asthma is a chronic disease characterized by airway inflammation, obstruction, and hyperresponsiveness. CD4+ T cells, particularly T helper (Th) 2 cells, and their specific cytokines are important mediators in asthma pathogenesis. However, it has been established that Th subsets, other than Th2, as well as various cell types, including innate lymphoid cells (ILCs), significantly contribute to the development of allergic inflammation. These cells require facilitated amino acid uptake to ensure their full function upon activation. Emerging studies have suggested the potential of pharmacological inhibition of amino acid transporters to inhibit T cell activation and the application of this strategy for treating immunological and inflammatory disorders. In the present review, we explore the possibility of targeting L-type amino acid transporter (LAT) as a novel therapeutic approach for bronchial asthma, including its steroid-resistant endotypes.

Pathogenic changes in group 2 innate lymphoid cells (ILC2) in intractable asthma

There is a certain population of intractable asthma patients, who can not be controlled by corticosteroid therapy. It has been suggested that 5-10% of asthma patients have been suffered from steroid resistance. Since it has been difficult to develop a steroid-resistant asthma model, the detailed mechanisms have been unclear. Recently, an intractable asthma model showing steroid insensitivity was developed by the author and colleagues. We found that pathogenic changes in type 2 innate lymphoid cells (ILC2) were induced in the intractable asthma. When ovalbumin (OVA) + Al(OH)3-sensitized BALB/c mice were intratracheally challenged with OVA at 5 μg/animal, development of airway remodeling as well as lung eosinophilia and neutrophilia were markedly suppressed by treatment with dexamethasone. In contrast, when increasing the dose of OVA for challenges to 500 μg/animal, those asthmatic responses turned to be steroid insensitive. When Th2 cells and ILC2 in the lung were stimulated in vitro, ILC2 produced larger amounts of type 2 cytokines than Th2 cells. Interestingly, amounts of type 2 cytokines produced by the steroid-insensitive model-derived ILC2 were significantly larger than those by the steroid-sensitive, and that the former ILC2 exhibited higher expression of thymic stromal lymphopoietin (TSLP) receptor and signal transducer and activator of transcription (STAT) 5a gene. Treatment with anti-IL-5 antibody improved the steroid sensitivity. Taken together, ILC2 have been transformed to be pathogenic in the intractable asthma. IL-5 hyper-produced from ILC2 may be involved in the development of steroid resistance. The molecules related to the above mentioned are expected to be targets for development of new therapeutic drugs for intractable asthma.

Possible therapeutic use of L-type amino acid transporter 1 (LAT1)-specific inhibitor for intractable asthma treatment

Bronchial asthma (asthma) is characterized by chronic airway inflammation, reversible obstruction, and hyperresponsive conditions. Although most asthma patients have been becoming controllable by virtue of inhaled corticosteroid (ICS), substantial number of patients still do not respond to the steroid-based therapy. Mast cells, eosinophils, and helper T (Th) 2 cells have been considered as key players in asthma pathogenesis. However, emerging studies have revealed that Th subsets other than Th2, as well as various other immune cells, significantly contribute to the development of steroid-resistant intractable asthma. T cells and other inflammatory cells require incorporating a large amount of nutrients such as amino acids and glucose to exhibit their full function following activation. Based on this remarkable character, it has recently been suggested that the pharmacological inhibition of amino acid transporters is promising for treating immunological and inflammatory disorders through the suppression of inflammatory cell activation. In this review, we explore the possible management of intractable asthma by developing a selective inhibitor for L-type amino acid transporter (LAT) 1.

Phenotype changes in group 2 innate lymphoid cells (ILC2) in a murine model of intractable asthma

Phenotype changes in group 2 innate lymphoid cells (ILC2) in a murine model of intractable asthma

Cytokine Imbalance in a 15-year-old Boy with Pandemic Influenza an Infection Requiring Extracorporeal Membrane Oxygenation

Acute severe asthma is an acute episode of intractable asthma that is poorly responsive to standard management. Acute respiratory failure or acute respiratory distress syndrome (ARDS) requiring ventilator support may be life-threatening. Although respiratory viral infections are responsible for most asthma exacerbations, the seasonal influenza virus has not been considered a risk factor. However, the 2009 H1N1 influenza A pandemic strain (pH1N1), which has resulted in numerous hospitalizations and mortalities worldwide, has been reported to be closely related to asthma exacerbation. Thus, with over 300 million people suffering from asthma worldwide, further studies are needed to protect this vulnerable population that is highly susceptible to pH1N1 infection. Dysregulation of Th1/Th2 cytokines may be involved in asthma exacerbation. We report the case of a paediatric patient with acute respiratory failure due to asthma exacerbation triggered by pH1N1 infection. The patient exhibited Th2 polarization in the acute phase of exacerbation and recovered from ARDS through timely ventilator support and subsequent extracorporeal membrane oxygenation. Further investigation regarding the mechanism of immune response in asthma exacerbations associated with pH1N1 infection may elucidate the optimal treatment for asthma.

Unusual longstanding intrabronchial foreign body masquerading as intractable bronchial asthma in an adult: Case report and literature review

Introduction and importanceTracheo-bronchial foreign body inhalation is a very common encounter in clinical practice among pediatric patients and rarely seen among adults. When inhalation of foreign bodies occurs in adults then it tends to lodge within the right bronchial tree but in children it lodges in the central airways.Case presentationWe present a 58 year old woman, known asthmatic for 20 years and non-smoker who presented to our clinic which history of chronic cough, wheezing and pulmonary infections that did not respond to regular antibiotics and the usual antiasthmatic medications. She reported to have inhaled a foreign body about 18 years earlier. Extraction of the foreign body was performed without complications.Clinical discussionA chest x-ray done was found to be normal and computerized tomography scan (CT scan) of the chest was ordered and revealed bronchial wall thickening with a calcified foreign body seen in the right intermediate bronchus.A combined rigid and flexible endoscopic bronchoscopy was performed and a chicken bone (measuring 2 cm × 1.5 cm) was extracted from the right intermediate bronchus with very minimal bleeding being encountered during and post bronchoscopy. Extraction of the foreign body was performed without complications. Post endoscopic intrabronchial foreign body removal, the patient recovered completely.ConclusionAn intrabronchial foreign body being masked for more than a decade by co-existent bronchial asthma is a rare encounter. Moreover, adult patients with chronic cough should be handled with caution to rule out the possibility of FB aspiration.

English

BACKGROUND The incidence of lung carcinomas is on rise and it is the second most common cause of death due to carcinomas in the West. Due to rise in air pollutants other lung diseases are also on rise. The use of cytological methods in the diagnosis of pathological lesions of respiratory tract has been generally acclaimed as one of its most successful application. Flexible fibre optic bronchoscope revolutionised respiratory cytology because techniques like broncho alveolar lavage, brush cytology, bronchial biopsy, and fine needle aspiration cytology (FNAC) have become easier and more acceptable, shifting the emphasis from advanced inoperable malignancy to use of cytology as first line diagnostic and management tool. Broncho alveolar lavage (BAL) which was originally developed as a therapeutic tool for pulmonary alveolar proteinosis, cystic fibrosis and intractable asthma also has gained acceptance and steady popularity as a tool for diagnosis of lung pathology. We wanted to analyse BAL examined in the Department of Pathology, Nehru Shatabdi Chikitsalaya (NSC), NCL and establish its utility as a diagnostic tool in our setup and reduce referral to higher centres. METHODS 36 BAL samples were examined from August 2006 to December 2007. Bronchoscopy was performed by ENT specialists among all patients who were not relieved by the medical treatment and their X-ray lung showed some findings, as an outdoor procedure. Patients were asked to come in an empty stomach, and X-ray chest was done before bronchoscopy. All bronchoscopies were performed under local anaesthesia (LA) except for a 2 yrs. old child. BAL fluid was subjected to cytological studies and Ziehl-Neelsen staining wherever required. RESULTS Out of 36 cases, nonspecific inflammation was seen in 13 cases, tuberculosis in 8 cases, where in three samples of sputum were negative for acid-fast bacillus (AFB) and BAL showed bacteria in many fields. Two cases were found to have aspergillosis, to rule out contamination, serum antibodies against aspergillosis were estimated which was very high ruling out contamination. Out of 8 cases of malignancy one was metastasis from mature teratoma testis. Two cases of adenocarcinoma (both females) and two cases of squamous cell carcinoma were found, in one case of adenocarcinoma and two cases of squamous cell carcinoma (SCC), BAL was found negative. No history was available regarding tobacco smoking in females with adenocarcinoma. CONCLUSIONS Study of BAL obtained by simple non-invasive technique has improved the diagnostic accuracy of lung diseases. Carcinomas can be diagnosed at an early operable stage. The combination of BAL with brush cytology increases the accuracy. To conclude, in all bronchoscopic examination BAL should be performed and should be subjected to microscopic examination irrespective of the age of patient. KEY WORDS Fiberoptic Bronchoscope, Lung, BAL, Tuberculosis, Adenocarcinoma Lung, SCC Lung

A new mechanism of bronchial hyperresponsiveness revealed by murine Th9 cell-transferred asthma model

Bronchial asthma is a complex disease involving various inflammatory cells and tissue constituent cells. The spread of inhaled corticosteroids is changing asthma into a controllable disease, though the existence of intractable patients implies new mechanisms for the development and deterioration of asthma. Based on the difference in the pathological condition (phenotypes) and molecular mechanism (endotypes), subdivision of disease understanding is recently progressing. Accordingly, various T cell subsets other than Th2 cells, which have been considered to play a major role for many years, are being implicated in the pathogenesis of asthma. Therefore, we aimed to deepen the understanding of the complex mechanisms of intractable asthma by reviewing the characteristics of allergic inflammation mediated by each T cell subset and the trend of therapeutic strategies targeting their representative functional molecules. Among them, recently identified Th9 cells were reported to induce asthma-like eosinophilic inflammation with bronchial hyperresponsiveness (BHR). These phenotypes resemble to Th2 cells-mediated airway inflammation, though we found that Th9 but not Th2 cell-dependent asthma model develops eosinophil-independent and steroid-resistant BHR. Here, we would like to introduce our recent findings and an approach to elucidate a new mechanism of BHR, based on antigen-specific T cell subset-transferred mouse models we have established.

A case report of home-visit rehabilitation for intractable asthma

A case report of home-visit rehabilitation for intractable asthma

Treatment for intractable asthma: bronchial thermoplasty

Bronchial Thermoplasty (BT) is an epoch-making treatment that reduces bronchial smooth muscle by using a bronchoscope to reach the basket catheter to the bronchus and directing high-frequency current directly into the bronchi. In GINA Guidelines 2019, BT is considered to be additional treatment at Step V (the most severe), and the evidence level is B. The Japanese guidelines (JGL) also added BT as a treatment for Step 4, but it is reserved because there are still unclear points regarding long-term efficacy and safety. In Japan, as of April 1, 2019, 672 treatments were performed at 123 institutions nationwide. The average age of patients was 54.1 years, but 84 cases were over 70 years old. The average value of %FEV1 was 78.2%, but there were 94 cases less than 60%. There were 32 cases that underwent BT treatment at our institution. Of them, 12 cases with progress up to one year later could be observed. The average age was 56.1 years old, and each of 6 men and women had a %FEV1 of 70.5%. One year later, AQLQ and %FEV1 improved, and the number of exacerbations decreased, but exhaled NO values increased. %FEV1 improvement might be due to poorer lung function (70.5% vs. 77.8%) and more BT activation (average 1.28 times AIR2) compared to the AIR2 trial. In terms of improvement in %FEV1, patients with moderate obstructive disorder from 50 to 80% responded well after BT treatment. In the near future, various new antibody preparations such as IL-4 / 13 antibody and anti-TSLP antibody are expected to be promoted. Therefore, we first consider whether these antibody preparations can be applied to patients with refractory asthma. We consider that BT is indicated only when there is no indication or no expected effect of antibody preparations. In other words, BT treatment is the last resort of intractable asthma, and it is the duty of medical professionals involved in BT treatment to be able to advocate when it is best to give BT to such patients.

Successful management of severe asthma in a young boy with eosinophilic chronic rhinosinusitis who received omalizumab: a case report

BackgroundThe incidence of chronic rhinosinusitis with nasal polyps has recently increased in Japan and other East Asian countries, and this disease is called eosinophilic chronic sinusitis (ECRS) in Japan. ECRS usually occurs in adults and is frequently accompanied by refractory bronchial asthma. However, its occurrence in children under 10 years of age is rare. Here, we present an unusual case of ECRS complicated by intractable asthma in an 8-year-old boy.Case presentationOral administration of prednisolone (10 mg/day) initially relieved the ECRS and bronchial asthma, but both returned during prednisolone dose reduction. Because nasal cavity-opening surgery was ineffective, oral administration prednisolone at 10 mg/day was continued. Pancytopenia was observed 16 months after the start of treatment, and the patient was admitted to our hospital. He was diagnosed with refractory cytopenia in childhood, but gradually improved after cyclosporine treatment. Although the dose of cyclosporine was therapeutic for asthma, it did not alleviate the asthma attacks, and the patient’s quality of life markedly decreased. We administered omalizumab even though its use was contraindicated by negative results in an inhalable antigen test. After the third administration of omalizumab, the asthma was better controlled and respiratory function improved; however, the nasal symptoms of ECRS persisted. Attempts to relieve these symptoms by increasing the therapeutic dose of omalizumab were only partially successful. We replaced omalizumab with mepolizumab; doing so slightly improved the sinusitis symptoms, but quality of life remained unsatisfactory. We repeated the nasal cavity-opening surgery. After surgery, the asthma and sinusitis were unchanged.ConclusionsOmalizumab effectively treated the severe combined asthma in a young patient, but its effect on sinusitis was insufficient. More cases and long-term follow-up data are needed to better evaluate the effectiveness of mepolizumab for treatment of ECRS.

Improvement of exertional dyspnea and breathing pattern of inspiration to expiration after bronchial thermoplasty

BackgroundBronchial thermoplasty (BT) is a bronchoscopic treatment that can ameliorate the symptoms of severe asthma. However, little is known about the mechanism by which BT improves exertional dyspnea without significantly changing the resting pulmonary function in asthmatics. To understand the mechanism, cardiopulmonary variables were investigated using cardiopulmonary exercise testing (CPET) in a patient with severe asthma before and after BT.Case presentationA 57-year-old Japanese man visited our hospital for consultation of the intractable asthma, which we managed with three treatment sessions of BT. Comparison of the findings pre-BT and at 1 year after BT demonstrated that (1) the resting tests for respiration showed no improvement in forced expiratory volume in 1 s, but the forced oscillation technique showed decreases in both inhalation and exhalation respiratory resistance values, and (2) the CPET results showed (i) improvement in exertional dyspnea, exercise endurance, and arterial oxygen saturation at the end of exercise; (ii) that the expiratory tidal volume exceeded the inspiratory tidal volume during exercise, which implied that a sufficient exhalation enabled longer inspiratory time and adequate oxygen absorption; and (iii) that an increase in respiratory frequency could be prevented throughout exercise.ConclusionsThis case report described a novel mechanism of BT in improving exertional dyspnea and exercise duration, which was brought about by ventilatory improvements related to the breathing pattern of inspiration to expiration.

The pathogenicity of IL-33 on steroid-resistant eosinophilic inflammation via the activation of memory-type ST2+CD4+ T cells

The lungs are the primary organs of the respiratory system in many animals and have unique epithelial barrier systems to protect the host from continuous invasion of various harmful particles, such as viruses and bacteria. IL-33, a member of the IL-1 family of cytokines, is released from epithelial cells in the mucosal organs and drives the type 2 immune response by activating a number of immune cells in cases of helminth infection. However, IL-33 derived from epithelial cells also causes various allergic diseases via the activation of ST2-positive immune cells, including memory-type (CD62Llow CD44hi ) ST2+ CD4+ T cells in the lung. Recent studies have revealed that the type 2 inflammation induced by IL-33 is steroid resistant. Steroid resistance causes severe chronic inflammatory diseases, such as intractable asthma. In this review, we will discuss the impact of ST2+ CD4+ T cells on shaping the pathology of IL-33-induced eosinophilic inflammation. We will also highlight the mechanism underlying steroid resistance in eosinophilic pneumonia. A better understanding of the cellular and molecular mechanisms underlying steroid resistance is crucial for the development of new therapeutic strategies for intractable allergic diseases.

The Churg-Strauss syndrome

The Churg-Strauss syndrome is a small vessel vasculitis associated with asthma and eosinophilia. It can sometimes present in unusual ways such as mononeuritis multiplex or subarachnoid hemorrhage. The various symptoms and signs are discussed, such as fever, skin lesions and allergic rhinitis. The sudden onset of blindness and deafness can occur. Cardiac involvement is common, but central nervous system lesions are rare. The diagnosis of the syndrome is based on clinical findings such as asthma, eosinophilia, neuropathy, and sinusitis, and it can certainly mimic conditions such as the Guillain-Barr´ e syndrome. The cause of the syndrome is uncertain, but studies have suggested that it may well be an autoimmune disease. However, an allergy may be only one of several mechanisms triggering symptoms. There seems to be no doubt that certain drugs, notably leukotriene-receptor antagonists, can be to blame, and so can eotoxin-3. Symptoms can respond to treatment with immunosupressive drugs, and since their introduction, the survival rate has been markedly increased. Trials with other drugs, such as rituximab and omalizumab are reported. In cases of intractable asthma, the diagnosis of this syndrome should be considered.

Japanese Guideline for Adult Asthma 2014.

Adult bronchial asthma (hereinafter, asthma) is characterized by chronic airway inflammation, reversible airway narrowing, and airway hyperresponsiveness. Long-standing asthma induces airway remodeling to cause intractable asthma. The number of patients with asthma has increased, and that of patients who die from asthma has decreased (1.5 per 100,000 patients in 2012). The aim of asthma treatment is to enable patients with asthma to lead a normal life without any symptoms. A good relationship between physicians and patients is indispensable for appropriate treatment. Long-term management with antiasthmatic agents and elimination of the causes and risk factors of asthma are fundamental to its treatment. Four steps in pharmacotherapy differentiate between mild and intensive treatments; each step includes an appropriate daily dose of an inhaled corticosteroid, varying from low to high. Long-acting β2-agonists, leukotriene receptor antagonists, and sustained-release theophylline are recommended as concomitant drugs, while anti-immunoglobulin E antibody therapy has been recently developed for the most severe and persistent asthma involving allergic reactions. Inhaled β2-agonists, aminophylline, corticosteroids, adrenaline, oxygen therapy, and others are used as needed in acute exacerbations by choosing treatment steps for asthma exacerbations depending on the severity of attacks. Allergic rhinitis, chronic obstructive pulmonary disease, aspirin-induced asthma, pregnancy, asthma in athletes, and cough-variant asthma are also important issues that need to be considered.

Abnormal vocal cord movement treated with botulinum toxin in patients with asthma resistant to optimised management

Abnormal vocal cord movement may coexist with asthma and cause additional upper/middle airway obstruction. The condition may be a form of muscular dystonia that could contribute to asthma resistant to optimised treatments. Botulinum toxin causes temporary paralysis of muscle and may be an effective local treatment that improves asthma control. In an observational study, we evaluated the benefits of unilateral vocal cord injection with botulinum toxin in 11 patients (total 24 injections). Subjects had asthma resistant to optimised treatment and abnormal vocal cord movement. Responses after botulinum toxin treatment were assessed using asthma control test (ACT) scores, vocal cord narrowing quantified by computerised tomography (CT) of the larynx and spirometry. Side-effects were recorded. ACT scores improved overall (9.1 ± 2.4 before and 13.5 ± 4.5 after treatment; difference 4.4 ± 4.2; P < 0.001). There was also an improvement in airway size on CT larynx (time below lower limit of normal at baseline 39.4 ± 37.63% and improved to 17.6 ± 25.6% after injection; P = 0.032). Spirometry was not altered. One patient experienced an asthma exacerbation but overall side-effects were moderate, chiefly dysphonia and dysphagia. Although a placebo effect cannot be ruled out, local injection of botulinum toxin may be an effective treatment for intractable asthma associated with abnormal vocal cord movement. Further mechanistic studies and a double-blind randomised controlled trial of botulinum toxin treatment are merited.

The Creative Transformation of Trauma: Marcel Proust'sIn Search of Lost Time

Hidden childhood trauma beneath poignant memories is a central aspect of In Search of Lost Time. Marcel Proust's magnum opus may be psychoanalytically understood as an extraordinary literary transformation of severe trauma and associated unconscious confiicts. Proust's nearly fatal childhood asthma and concomitant medical mistreatment contributed to an intense ambivalent bond and bondage with his mother, replicated in the ambivalent relationships depicted in his novel. The retrieved and re-created past is relived in the novel's fantasy playground of time and space. Proust's intuitive grasp of signiflcant aspects of time, memory, trauma, and transference was consistent with psychoanalytic thought. In the vast novel, the narcissistic mortiflcation and losses of the protagonist are mourned, worked through, and partially redeemed. I interpret the famed joyous tasting of the madeleine in tea as an artfully disguised, temporally displaced, and affective reversal of life-threatening trauma. This article probes the role of Proust's intractable asthma in his breathless journey to ego mastery and timeless creativity.

EComment. Mucoepidermoid carcinoma: common findings and surgical treatment

We read with interest the paper by Papiashvilli and co-authors, reporting on an interesting case of mucoepidermoid carcinoma of the lower trachea in a 9-year old boy [1]. Mucoepidermoid carcinomas are rare neoplasms [2] of the bronchial tree arising from mucous and serous glands of the epithelium. They are rare and represent about 1% to 5% of bronchial adenomas, including also adenoid cystic carcinomas (cylindromas), mucous gland adenomas and carcinoids. The term “bronchial adenomas” is not correct because it refers to a benign process, and experience has demonstrated that these tumours have a broad spectrum of biologic activity and can sometimes have malignant behaviour. The term “bronchial adenomas” has therefore been recently replaced by “bronchial gland tumours”. These slow-growing tumours usually manifest with irritation and obstruction of the tracheobronchial tree and symptoms are related to their site [3]. When these masses are located in the trachea, as with the case presented by Papiashvilli et al, they produce upper respiratory tract occlusion with cough, wheezing and dyspnea. In this young patient, respiratory distress was interpreted as asthma until a CT scan showed the tracheal obstruction. Tracheal obstruction must always be suspected in intractable asthma, also in young patients. In cases of localization in the proximal or segmental bronchi, symptoms are usually related to progressive occlusion of a bronchus and therefore are characterized by relapsing pneumonia. Complete surgical resection is the treatment of choice for mucoepidermoid carcinoma. Endoscopic resection has been attempted, but the incidence of local relapse is high. It has a role only as a temporary option in order to plan and facilitate surgery. The principles of surgery are a clear margin at frozen section, complete locoregional lymph nodes removal and maximum sparing of lung parenchyma with tracheobronchial resection and reconstruction techniques. In the case reported by Papiashvilli and co-workers they performed an excellent and successful operation through a sternotomy, which is an unusual access to the lower trachea. As reported by the authors, the choice was based on “difficulty ventilating the child” and “the existence of immediate cardiopulmonary by-pass facilities”. Being general thoracic surgeons, we would have made the same operation through a right thoracotomy, and would have been ready to use a partial by-pass with peripheral cannulation, if required. We appreciate the report of such an unusual case successfully treated in a young boy. Conflict of Interest: None declared

A Patient with Relapsing Polychondritis who Had Been Diagnosed as Intractable Bronchial Asthma

A 62-year-old woman, diagnosed as bronchial asthma 3 years previously, was admitted due to acute severe dyspnea. Physical examination revealed saddle nose, flare/swelling of the ear auricles, and stridor. Computed tomography demonstrated thickening of tracheal/bronchial walls and stenosis of the lumen that deteriorated on expiration, suggesting tracheobronchomalacia. Auricle biopsy indicated cartilage destruction. Based on these findings, the patient was diagnosed as relapsing polychondritis. As demonstrated in this case, relapsing polychondritis involving airways might be misdiagnosed as bronchial asthma due to stridor and transient corticosteroid-related improvement. Early diagnosis is necessary to prevent irreversible airway stenosis and progression to tracheobronchomalacia.

Stress-related asthma and family therapy: Case study

This paper applies the Biobehavioral Family Model (BBFM) of stress- related illness to the study and treatment of an adolescent with intractable asthma. The model is described, along with supportive research findings. Then a case study is presented, demonstrating how the model is clinically applied. We tell the story of an asthmatic adolescent presenting for therapy due to her intense asthmatic crises, and the case is presented to exemplify how the BBFM can help understand the family-psychobiological contribution to exacerbation of disease activity, and therefore guide treatment towards the amelioration of severe physical symptoms. Facets of the patient’s intra-familial interactions are consistent with the BBFM, which support clinical validation of the model. In the case described, it is likely that additional asthma medications would not have had the desired ameliorative effect, because they did not target the family relational processes contributing to the symptoms. The recognition of the influences of family relational processes on the disease was crucial for effective intervention. The therapy incorporates and weaves together BBFM understanding of family patterns of interaction and physiological/medical concerns integrated with Bowenian intervention strategies. This case study validates the importance and usefulness of BBFM for intervention with stress-sensitive illnesses such as asthma.