reactive airways dysfunction syndrome ( rads ) is defined as the sudden onset of asthma - like symptoms following high - level exposure to a corrosive gas , vapor , or fumes . the term rads was originally described by brooks and lockers in 19811 as nonimmunological asthma resulting from exposure to an irritant gas . given that most cases are recognized retrospectively , often with considerable delay , they usually lack accurate assessment of the exposure intensity and objective evidence of prior normal bronchial hyper - responsiveness required for the diagnosis of rads.2 the symptoms usually manifest within 24 hours of exposure as bronchitis , with ocular or mucus membrane irritation of the upper airway ( depending on the agent ) and often require emergency treatment . the presentation of rads is different from that of true occupational asthma , because it is an acute single event without a significant latency period . many cases occurred after the 9/11 collapse of the new york world trade center , resulting from the inhalation of fumes and particulate matter.3 the american college of chest physicians consensus criteria for the diagnosis of rads were agreed in 1995,4 and were : 
 documented absence of preceding respiratory complaintonset after single exposure incident / accidentexposure to very high concentration of gas , smoke , fumes , or vapors with irritant propertiesonset of symptoms within 24 hours after exposure with persistence for at least 3 monthssymptoms that simulate asthma with cough , wheeze , and dyspneapresence of airflow obstruction on pulmonary function  nonspecific bronchial hyper - responsivenessall other pulmonary disease excluded . documented absence of preceding respiratory complaint onset after single exposure incident / accident exposure to very high concentration of gas , smoke , fumes , or vapors with irritant properties onset of symptoms within 24 hours after exposure with persistence for at least 3 months symptoms that simulate asthma with cough , wheeze , and dyspnea presence of airflow obstruction on pulmonary function  nonspecific bronchial hyper - responsiveness all other pulmonary disease excluded . these criteria have been criticized for being overly restrictive by alberts and do pico.5 the pathology of rads shows nonspecific inflammation , with a cellular infiltrate which is primarily lymphocytic with epithelial desquamation.6 alberts and brooks describe the  big bang  mechanism of epithelial injury , with activation of nonadrenergic and noncholinergic fibers via axon reflexes giving rise to neurogenic inflammation , macrophage activation , and mast cell degranulation.7 the resulting proinflammatory state , with toxic mediators , gives rise to epithelial injury . although most people recover , extensive inflammation and epithelial sloughing could reduce receptor thresholds for severe ongoing bronchial hyper - reactivity . to date the literature suggests that rads should be recognized as a unique form of asthma with significant upper airway symptoms that are often ignored but appear to be part of the condition.8 there is a growing list of recognized causal agents,9 which include : 
 household exposure : floor sealants , spray paint , bleaching agents , household cleaners containing morpholine.chemical : chlorine , sulphuric acid , ammonia , hydrochloric acid , acetic acid , phosgene , hydrogen sulphide , sodium azide , sodium hypochlorite , toluene di - isocyanates , organic solvents.industry : paint spraying , metal - coat removers , welding , heated plastics or acids , epoxy resins , perfumes , pesticides , enzymes , industrial cleaning products , dust or molds in silos.other : fire and smoke inhalation , burning paint fumes , tear gas , locomotive exhaust , world trade center collapse in new york . household exposure : floor sealants , spray paint , bleaching agents , household cleaners containing morpholine . chemical : chlorine , sulphuric acid , ammonia , hydrochloric acid , acetic acid , phosgene , hydrogen sulphide , sodium azide , sodium hypochlorite , toluene di - isocyanates , organic solvents . industry : paint spraying , metal - coat removers , welding , heated plastics or acids , epoxy resins , perfumes , pesticides , enzymes , industrial cleaning products , dust or molds in silos . other : fire and smoke inhalation , burning paint fumes , tear gas , locomotive exhaust , world trade center collapse in new york . traditional treatment is the same as that of conventional asthma , despite evidence that patients with rads are less responsive to 2 agonists.10 long - term outcome is not well documented , but if symptoms do not remit within 624 months they are more likely to become persistent.11 oral corticosteroids and bronchodilators commenced within the first 3 months have had the most favorable outcomes.12,13 however , some reported case series suggest symptoms may be more persistent than originally thought . demeter et al14 reported a nine - year follow - up , where nine of 19 patients with rads still had ongoing symptoms , one of whom was progressive . malo assessed mill workers following exposure to chlorine , and found that 29 of 51 still had bronchial hyper - responsiveness over a period of 24 months.15 there is a paucity of data regarding therapeutic interventions for those with persistent symptoms . nebulized sodium bicarbonate following chlorine gas exposure has been shown to improve quality of life and forced expiratory volume in 1 second ( fev1),16 but not lead to a resolution of symptoms . lung transplantation has been used for severe ongoing symptoms of rads following the new york world trade center collapse.17 this report describes a patient with severe unremitting symptoms of rads five years following ammonia exposure , and discusses the response to vitamin d. a 36-year - old nursing sister was referred to our center with a history of incessant cough , shortness of breath , and extreme bronchial hyper - reactivity of five years duration . symptoms had started following exposure to an ammonia spillage by workmen on the floor below the renal unit where she worked as a dialysis sister . the unit had to be evacuated and she received high level exposure for up to two hours . later that day she developed acute onset of cough , wheeze , and mucosal irritation symptoms , and needed to attend accident and emergency . initially this produced an improvement in symptoms ; however , over the subsequent year she required multiple courses of prednisolone , and commenced inhaled corticosteroids and a short - acting 2 agonist . she was seen at a specialist chest hospital , but no solution or effective treatment was found , and pessimism developed about a likely response to any treatment . her original assessment showed normal routine blood tests , a clear chest radiograph , normal echocardiogram , and normal high - resolution computed tomography of her chest . pulmonary function tests had revealed evidence of airways obstruction with airway resistance ( raw ) at 168% of predicted and reduced small airway indices . histamine challenge was positive , with a methacholine - provoking concentration for a 20% fall ( pc20 ) of 7.3 mg / ml . the patient was unable to return to work , and had become virtually housebound due to the severity of her symptoms and the speed and intensity of her bronchospasm to outside odors . she had no prior respiratory illness , no atopy , and was a lifelong nonsmoker . five years later , at the time of her referral to our center , her life quality was extremely poor . she was experiencing intractable paroxysms of coughing lasting continuously for 45 hours , with an incessant background cough leading to significant chest wall pain . she recognized multiple triggers , including air temperature changes , cigarette smoke , perfumes , cleaning products , exertion , and laughing . she suffered from dyspnea secondary to the coughing both at rest and on exertion due to her level of bronchial hyper - reactivity . in terms of medication , she was taking high - dose inhaled pulmicort , formoterol , ipratropium , and regular nonsteroidal anti - inflammatory analgesia and tramadol for chest wall pain , along with omeprazole . she fulfilled all clinical criteria for the diagnosis of rads.1 a repeat of her tests was impossible due to her intractable coughing . however , she did undergo a bronchoscopy at our center , which showed the entire bronchial tree mucosa to be deeply erythematous with widespread petechial hemorrhage . due to the irritant effects of the disinfectants in the endoscopy suite , severe aggravation of her coughing occurred on her arrival , making the procedure very difficult , and precluding the chance of a biopsy . g / l ) without any other immune defect , and intravenous immunoglobulin ( vigam ) was given without benefit . antiviral drugs were tried followed by cotrimoxazole without benefit , with trials lasting several weeks . this appeared to increase her symptoms by 3 months , and at 4 months it was discontinued . this completed at least 12 months of trials with different treatments , without any hint of improvement . at this stage , the immunological properties of vitamin d were being reported , and we began a trial of high - dose oral vitamin d 2000 iu / day . vitamin d levels were requested , but her local hospital did not routinely perform this test . as a result , scientific data from osteoporosis research shows a rise of 810 nmol each month on a vitamin d dose of 1000 iu / day . this would suggest that our patient s vitamin d level was < 25 nmol / l , initially consistent with severe deficiency . history - taking confirmed no ingestion of oily fish and no sunlight exposure or sunbathing for many years . at the start of vitamin d therapy , her symptoms were severe with incessant cough and bronchial hyper - reactivity as described before , which made measurement of formal lung function difficult . her chest remained clear on physical examination , and she had a c - reactive protein of 0.2 and an immunoglobulin e of 9 ku / l . despite no other adjustment to her regular medication regime , she noticed an improvement in her symptoms once her 25-hydroxyvitamin d blood levels were > 100 initially the paroxysms of cough abated , followed by resolution of dyspnea on exertion at vitamin d levels > 150 nmol / l . we were then able to measure formal lung function tests reliably for the first time . her vitamin d levels took 6 months to rise to 200 nmol / l . at that point symptoms resolved , and weaning of nebulizers , steroids , nonsteroidal anti - inflammatory drugs , and other painkillers could commence , because chest wall pains due to incessant cough eased . figure 1 demonstrates her serum vitamin d levels , and highlights the symptomatic improvement and spirometry . at two years her lung function tests one year later are normal ( forced vital capacity 117% , vital capacity 100% , tlco ( transfer factor of the lung for carbon monoxide ) 97% , forced expiratory flow 25%75% 110% ) , apart from a residual volume of 182% of predicted which has remained unchanged on several repeat measurements . a recent methacholine test gave a pc20 of 32 mg / ml . high - dose vitamin d has been continued and blood levels have remained at 150200 nmol / l with normal calcium levels . there are no reported adverse effects of regular vitamin d at doses of up to 5000 iu / day . there were no side effects of the vitamin d , but oral preparations are known to have a mild laxative effect and increase skin oils that may cause spots . we all live or work in an increasingly chemical environment , where uncontrolled inhalational exposures to toxic materials could affect our respiratory system acutely . the risk of toxic household cleaning products , paints , and resins may not be well recognized by the general public , unlike that in industry where risk assessments are paramount . rads is a condition which currently lacks clarity,2,18 with the main difficulties related to retrospective diagnosis of a condition following an unmeasured exposure to a respiratory irritant . animal models to establish the exact nature and natural history are still awaited , but should assist our understanding of whether this is an asthma variant or a different disease state . while the literature contains increasing numbers of reported cases from an expanding array of causal agents , it lacks any guidance on effective treatment , especially for those patients with ongoing symptoms who have a very poor quality of life . the effects of vitamin d as a hormone have gained attention in the literature over the last 23 years . vitamin d appears to have regulatory effects on every part of the immune system , with vitamin d deficiency being linked to an array of immunologically based diseases.19 because vitamin d promotes steroid sensitivity in the body and can downregulate an inflammatory state via gene expression and cytokine production , its action in this case could be directly on the airway . vitamin d receptors are present in the airways and are thought to inhibit proinflammatory cytokines , with effects on cd4 + t cells , interleukin-2 , interferon - gamma , and macrophages.20,21 a deficiency of vitamin d could be associated with an inability to switch off the inflammatory state , following an acute inhalational insult , with upregulation of prostaglandin , leukotrienes , macrophages , and t cell activity and recruitment . vitamin d receptor polymorphisms are gaining attention as a cause of vitamin d insensitivity in respiratory diseases , which can be overcome by high doses . in our case , vitamin d deficiency was present because optimal blood levels should be > 75 nmol / l . we had no histological biopsies from our case , but considered her to fulfill all criteria for rads . this case presented a difficult management problem , and was refractory to all conventional treatments , with devastating effects on employment . the responses to vitamin d were slow and progressive , and effects appeared optimal when blood levels were > 150 nmol / l . these observations would support a trial of high - dose oral vitamin d in similar cases of rads refractory to asthma treatment . if this experience is repeated , it may assist our understanding of the condition and possible disease mechanisms , via the anti - inflammatory effects of vitamin d , and offer a treatment .