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The main objective of this study was to examine the perception of the first symptom during methacholine bronchoconstriction as soon as it occurred, and in the second instance to quantify the intensity of the breathlessness by means of the Borg Scale performed at the end of challenge so to not determine any difficulties for identification of the first symptom. A methacholine challenge test was carried out in 139 symptom-free asthmatics with a normal pulmonary function. When the first symptom was reported by the subject, the forced expiratory volume in one second (FEV1) was measured immediately. FEV1 was expressed as a percentage of the best personal value (FEV1%BPV). The intensity of the breathlessness was rated using a modified Borg Scale at the end of the challenge test so as not to confuse the patient. Seven subjects felt nothing during challenge. The first symptoms varied: constriction behind the breastbone (49%), inspiratory shortness (16.5%), coughing (10%), wheezing, throat constriction, general chest tightness, pain behind the sternum, and a sensation of rheum behind the sternum. FEV1%BPV at the first symptom was 80.5 +/- 10 (range 41-99). No symptom was perceived by 42% of the subjects within the 80-100 range of FEV1%BPV. FEV1%BPV at the first symptom was related to the log of the provocative dose causing a 20% fall in FEV1 (r = 0.2, p < 0.05). An inverse correlation between Borg Score and final FEV1%BPV (r = -0.25, p < 0.01) was found at the end of challenge. A subgroup of 39 subjects with similar final FEV1%BPV values (68-72) showed a correlation between the Borg Score at end of challenge and FEV1%BPV at the first symptom (r = 0.59, p < 0.001). The first symptom of the methacholine-induced bronchoconstriction varies in asthmatics and may be atypical, the bronchoconstriction level at which it is felt also varies among individuals, highly methacholine-responsive subjects perceive the bronchoconstriction later, while late perceivers of the first symptom show less intense breathlessness at the end of challenge. The measurement of the patient's ability to perceive asthmatic symptoms during the methacholine challenge test could be used to single out poor perceivers.
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PMID:Perception of methacholine-induced airway obstruction in asthmatics. 1121 71

Gastroesophageal reflux (GER) is a factor often neglected in the etiopathogenesis of asthma. The estimated incidence of GER in asthmatic children reaches 50-60% and is higher than in the general population. GER may accompany typical symptoms: hoarseness, sore throat, thoracic pain, cough or wheezing. GER may not only aggravate the course of bronchial obstruction, but may also cause it, or trigger obstruction due to other factors. Asthma and GER coincidence has been acknowledged for many years. The paper presents a current review of studies concerning the relations between asthma and GER and attempts to establish, which is the cause and which is the result. The hypotheses how GER can lead to bronchial obstruction, and how obstruction can aggravate GER, are also presented. GER is believed to be a factor causing obstruction by: 1. an indirect mechanism - reflex theory, 2. a direct mechanism - reflux theory, and 3. a neuropeptide-mediated mechanism. The paper also presents diagnostic methods allowing to detect GER in asthmatics. A review of recent studies concerning the treatment of GER in asthmatics, both with pharmacological and surgical methods, is also included. Beneficial effect of antireflux therapy on the course of asthma has been emphasized. Therefore, antireflux therapy is recommended in all patients with concurrent asthma and GER, irrespective of severity of clinical GER symptoms, even in those with silent GER. The essential drugs used in the treatment of GER are proton pump inhibitors. Appropriately high dose level and appropriately long duration of the therapy should be taken into consideration.
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PMID:Asthma and gastroesophageal reflux in children. 1188 43

Pulmonary Embolism (PE) poses an important diagnostic problem in patients with chronic obstructive pulmonary disease (COPD). Indeed PE may aggravate the already precarious respiratory state of these fragile patients. Moreover, these two conditions share common symptoms: dyspnoea, wheezing, pleural pain, haemoptysis, palpitations and signs of right cardiac insufficiency. In two studies, one retrospective and the other prospective, we investigated the incidence of PE in patients with non-infective exacerbations of their COPD. The retrospective study was carried out over two years and involved 50 COPD patients with non-infective respiratory exacerbations. In this population, 10 patients out of 50 (20%) had a documented PE. No predictive factor was identified. The prospective study was conducted over one year and COPD patients admitted to hospital with exacerbations were included in the study if they had a positive D-dimer blood test and no evidence of acute respiratory infection. 31 patients were studied with Doppler ultra-sound examination of the legs and a lung perfusion scan. The presence or absence of PE was determined and the two groups were compared. 9 patients out of 31 (29%) had a documented PE. Six of these nine patients had a deep venous thrombosis (DVT). Two predictive factors of PE were identified: existence of a DVT and a significant fall in PaO(2) from baseline state (DeltaPaO(2) > 22 mmHg). We conclude that PE is a frequent (20 to 30%) of non-infective respiratory decompensation in COPD patients. Faced with an unexplained respiratory exacerbation in these patients, a lung perfusion scan should be routinely undertaken to rule out a PE when the D-dimers are positive.
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PMID:[Pulmonary embolism and sibilant types of chronic obstructive pulmonary disease decompensations]. 1241 52

The gastroesophageal reflux disease (GERB) is one from the most frequent disease of the upper gastrointestinal system. Extraesophageal manifestations GERB occur most often as lung manifestations, ORL discomforts, and as noncardial pain in breasts. GERB is associated with the various respiratory diseases and symptoms as are the bronchial asthma, cough, wheezing. The episodes of the sour reflux into the esophagus, specially in children, can provoke the symptoms discapper mainly in all patients who have used the antisecretoral therapy.
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PMID:[Extraesophageal manifestations of gastroesophageal reflux]. 1282 64

Ketorolac is a potent analgesic drug that has been restricted in dosage and use because of its potential adverse effects. The diagnostic and ethical challenges of 2 children who had unpredictable adverse drug reactions to ketorolac are reported. Case 1: A 3-year-old boy received ketorolac 1 mg/kg for prevention of postoperative pain at the end of an orthopedic surgical procedure. Ten minutes later, he had bilateral palpebral edema, erythema in thorax, hypotension, and tachycardia. The adverse event was classified as a mixed reaction probably related to ketorolac. Case 2: A 7-year-old girl, who had previously received ketorolac in 2 different surgical procedures, underwent a third orthopedic surgery. She received ketorolac 1 mg/kg as pre-emptive analgesia at 1.5 hours of anesthetic time (approximately 1 hour of surgical time). The patient developed palpebral edema 5 minutes later in addition to erythema in thorax, hypotension, tachycardia, tachypnea, oxygen desaturation, and wheezing. The adverse event was classified as a systemic reaction probably related to ketorolac. The 2 patients were successfully treated with symptomatic therapy. Although rare in its frequency, ketorolac administration may be associated to anaphylactic and anaphylactoid reactions in children with or without history of previous exposure. Because ketorolac is off-licensed for pediatric patients, it should be administered only after the risks and benefits have been discussed with the child's parents in the preanesthetic consultation.
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PMID:Report of an anaphylactoid and an anaphylactic reaction to ketorolac in two pediatric surgical patients. 1677 34

Capsicum-derived ingredients function as skin-conditioning agents--miscellaneous, external analgesics, flavoring agents, or fragrance components in cosmetics. These ingredients are used in 19 cosmetic products at concentrations as high as 5%. Cosmetic-grade material may be extracted using hexane, ethanol, or vegetable oil and contain the full range of phytocompounds that are found in the Capsicum annuum or Capsicum frutescens plant (aka red chiles), including Capsaicin. Aflatoxin and N-nitroso compounds (N-nitrosodimethylamine and N-nitrosopyrrolidine) have been detected as contaminants. The ultraviolet (UV) absorption spectrum for Capsicum Annuum Fruit Extract indicates a small peak at approximately 275 nm, and a gradual increase in absorbance, beginning at approximately 400 nm. Capsicum and paprika are generally recognized as safe by the U.S. Food and Drug Administration for use in food. Hexane, chloroform, and ethyl acetate extracts of Capsicum Frutescens Fruit at 200 mg/kg resulted in death of all mice. In a short-term inhalation toxicity study using rats, no difference was found between vehicle control and a 7% Capsicum Oleoresin solution. In a 4-week feeding study, red chilli (Capsicum annuum) in the diet at concentrations up to 10% was relatively nontoxic in groups of male mice. In an 8-week feeding study using rats, intestinal exfoliation, cytoplasmic fatty vacuolation and centrilobular necrosis of hepatocytes, and aggregation of lymphocytes in the portal areas were seen at 10% Capsicum Frutescens Fruit, but not 2%. Rats fed 0.5 g/kg day-1 crude Capsicum Fruit Extract for 60 days exhibited no significant gross pathology at necropsy, but slight hyperemia of the liver and reddening of the gastric mucosa were observed. Weanling rats fed basal diets supplemented with whole red pepper at concentrations up to 5.0% for up to 8 weeks had no pathology of the large intestines, livers, and kidneys, but destruction of the taste buds and keratinization and erosion of the gastrointestinal (GI) tract were noted in groups fed 0.5% to 5.0% red pepper. The results of 9-and 12-month extension of this study showed normal large intestines and kidneys. In rabbits fed Capsicum Annuum Powder at 5 mg/kg day-1 in the diet daily for 12 months damage to the liver and spleen was noted. A rabbit skin irritation test of Capsicum Annuum Fruit Extract at concentrations ranging from 0.1% to 1.0% produced no irritation, but Capsicum Frutescens Fruit Extract induced concentration-dependent (at 25 to 500 microg/ml) cytotoxicity in a human buccal mucosa fibroblast cell line. An ethanol extract of red chili was mutagenic in Salmonella typhimurium TA98, but not in TA100, or in Escherichia coli. Other genotoxicity assays gave a similar pattern of mixed results. Adenocarcinoma of the abdomen was observed in 7/20 mice fed 100 mg red chilies per day for 12 months; no tumors were seen in control animals. Neoplastic changes in the liver and intestinal tumors were observed in rats fed red chili powder at 80 mg/kg day-1 for 30 days, intestinal and colon tumors were seen in rats fed red chili powder and 1,2-dimethyl hydrazine, but no tumors were observed in controls. In another study in rats, however, red chile pepper in the diet at the same dose decreased the number of tumors seen with 1,2-dimethylhydrazine. Other feeding studies evaluated the effect of red chili peppers on the incidence of stomach tumors produced by N-methyl-N'-nitro-N-nitrosoguanidine, finding that red pepper had a promoting effect. Capsicum Frutescens Fruit Extract promoted the carcinogenic effect of methyl(acetoxymethyl)nitrosamine (carcinogen) or benzene hexachloride (hepatocarcinogen) in inbred male and female Balb/c mice dosed orally (tongue application). Clinical findings include symptoms of cough, sneezing, and runny nose in chili factory workers. Human respiratory responses to Capsicum Oleoresin spray include burning of the throat, wheezing, dry cough, shortness of breath, gagging, gasping, inability to breathe or speak, and, rarely, cyanosis, apnea, and respiratory arrest. A trade name mixture containing 1% to 5% Capsicum Frutescens Fruit Extract induced very slight erythema in 1 of 10 volunteers patch tested for 48 h. Capsicum Frutescens Fruit Extract at 0.025% in a repeated-insult patch test using 103 subjects resulted in no clinically meaningful irritation or allergic contact dermatitis. One epidemiological study indicated that chili pepper consumption may be a strong risk factor for gastric cancer in populations with high intakes of chili pepper; however, other studies did not find this association. Capsaicin functions as an external analgesic, a fragrance ingredient, and as a skin-conditioning agent--miscellaneous in cosmetic products, but is not in current use. Capsaicin is not generally recognized as safe and effective by the U.S. Food and Drug Administration for fever blister and cold sore treatment, but is considered to be safe and effective as an external analgesic counterirritant. Ingested Capsaicin is rapidly absorbed from the stomach and small intestine in animal studies. Subcutaneous injection of Capsaicin in rats resulted in a rise in the blood concentration, reaching a maximum at 5 h; the highest tissue concentrations were in the kidney and lowest in the liver. In vitro percutaneous absorption of Capsaicin has been demonstrated in human, rat, mouse, rabbit, and pig skin. Enhancement of the skin permeation of naproxen (nonsteroidal anti-inflammatory agent) in the presence of Capsaicin has also been demonstrated. Pharmacological and physiological studies demonstrated that Capsaicin, which contains a vanillyl moiety, produces its sensory effects by activating a Ca2 +-permeable ion channel on sensory neurons. Capsaicin is a known activator of vanilloid receptor 1. Capsaicin-induced stimulation of prostaglandin biosynthesis has been shown using bull seminal vesicles and rheumatoid arthritis synoviocytes. Capsaicin inhibits protein synthesis in Vero kidney cells and human neuroblastoma SHSY-5Y cells in vitro, and inhibits growth of E. coli, Pseudomonas solanacearum, and Bacillus subtilis bacterial cultures, but not Saccharomyces cerevisiae. Oral LD50 values as low as 161.2 mg/kg (rats) and 118.8 mg/kg (mice) have been reported for Capsaicin in acute oral toxicity studies, with hemorrhage of the gastric fundus observed in some of the animals that died. Intravenous, intraperitoneal, and subcutaneous LD50 values were lower. In subchronic oral toxicity studies using mice, Capsaicin produced statistically significant differences in the growth rate and liver/body weight increases. Capsaicin is an ocular irritant in mice, rats, and rabbits. Dose-related edema was observed in animals receiving Capsaicin injections into the hindpaw (rats) or application to the ear (mice). In guinea pigs, dinitrochlorobenzene contact dermatitis was enhanced in the presence of Capsaicin, injected subcutaneously, whereas dermal application inhibited sensitization in mice. Immune system effects have been observed in neonatal rats injected subcutaneously with Capsaicin. Capsaicin produced mixed results in S. typhimurium micronucleus and sister-chromatid exchange genotoxicity assays. Positive results for Capsaicin were reported in DNA damage assays. Carcinogenic, cocarcinogenic, anticarcinogenic, antitumorigenic, tumor promotion, and anti-tumor promotion effects of Capsaicin have been reported in animal studies. Except for a significant reduction in crown-rump length in day 18 rats injected subcutaneously with Capsaicin (50 mg/kg) on gestation days 14, 16, 18, or 20, no reproductive or developmental toxicity was noted. In pregnant mice dosed subcutaneously with Capsaicin, depletion of substance P in the spinal cord and peripheral nerves of pregnant females and fetuses was noted. In clinical tests, nerve degeneration of intracutaneous nerve fibers and a decrease in pain sensation induced by heat and mechanical stimuli were evident in subjects injected intradermally with Capsaicin. An increase in mean inspiratory flow was reported for eight normal subjects who inhaled nebulized 10(-7) M Capsaicin. The results of provocative and predictive tests involving human subjects indicated that Capsaicin is a skin irritant. Overall, studies suggested that these ingredients can be irritating at low concentrations. Although the genotoxicity, carcinogenicity, and tumor promotion potential of Capsaicin have been demonstrated, so have opposite effects. Skin irritation and other tumor-promoting effects of Capsaicin appear to be mediated through interaction with the same vanilloid receptor. Given this mechanism of action and the observation that many tumor promoters are irritating to the skin, the Panel considered it likely that a potent tumor promoter may also be a moderate to severe skin irritant. Thus, a limitation on Capsaicin content that would significantly reduce its skin irritation potential is expected to, in effect, lessen any concerns relating to tumor promotion potential. Because Capsaicin enhanced the penetration of an anti-inflammatory agent through human skin, the Panel recommends that care should be exercised in using ingredients that contain Capsaicin in cosmetic products. The Panel advised industry that the total polychlorinated biphenyl (PCB)/pesticide contamination should be limited to not more than 40 ppm, with not more than 10 ppm for any specific residue, and agreed on the following limitations for other impurities: arsenic (3 mg/kg max), heavy metals (0.002% max), and lead (5 mg/kg max). Industry was also advised that aflatoxin should not be present in these ingredients (the Panel adopted < or =15 ppb as corresponding to "negative" aflatoxin content), and that ingredients derived from Capsicum annuum and Capsicum Frutescens Plant species should not be used in products where N-nitroso compounds may be formed. (ABSTRACT TRUNCATED)
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PMID:Final report on the safety assessment of capsicum annuum extract, capsicum annuum fruit extract, capsicum annuum resin, capsicum annuum fruit powder, capsicum frutescens fruit, capsicum frutescens fruit extract, capsicum frutescens resin, and capsaicin. 1736 37

Although chronic obstructive pulmonary disease (COPD) is a highly prevalent and disabling illness, few empirical studies have evaluated the impact of the disease on symptom distress, functional status, and quality of life. These outcomes were explored in a prospective survey of 100 patients with advanced COPD. Patients were recruited from two academic centers. The mean forced expiratory volume in 1 second (FEV1) was 24.4% (standard deviation=3.9). Validated instruments were used to assess symptom distress (Memorial Symptom Assessment Scale [MSAS]), mental health (Mental Health Inventory [MHI]-5), functional status (Sickness Impact Profile [SIP]), quality of life (Multidimensional Index of Life Quality [MILQ]), spirituality (Functional Assessment of Chronic Illness Therapy [FACIT] Spirituality Scale), and comorbid conditions (Charlson Comorbidity Index). The most prevalent symptoms were dyspnea (94%), fatigue (71%), xerostomia (60%), coughing (56%), and anxiety (51%). Other symptoms with high prevalence were drowsiness (47%), irritability (42%), feeling nervous (40%), and wheezing (40%). Significant pain was reported in about one-third of patients. Patients reported relatively high levels of overall functional impairment (SIP median=24.0) and modest impairment in overall quality of life (MILQ median=52). Overall, psychological well-being was relatively unimpaired (median=24.5), and the comfort derived from faith was intact (FACIT median=2.5). Impairment in quality of life was strongly associated with symptom distress (MSAS-GDI; r=-0.74, P<0.001), functional impairment (SIP total; r=-0.59, P<0.001), female sex (r=-0.26, P=0.01), and poor psychological well-being (MHI-5; r=0.68, P<0.001). In multivariate analyses, poor quality of life was strongly correlated with higher total symptom distress, sickness-related dysfunction, and lower levels of psychological well-being (R(2)=0.66). In addition, two specific psychological symptoms-worrying and feeling irritable-were independently predictive of poor quality of life. Patients with advanced COPD have multiple distressing symptoms and a high prevalence of disturbances in mood, functional status, and quality of life. A focus on ameliorating prevalent physical symptoms and psychological distress may lead to an improvement in the overall quality of life in this patient population.
J Pain Symptom Manage 2009 Jul
PMID:Symptom distress and quality of life in patients with advanced chronic obstructive pulmonary disease. 1923 93

A physician diagnosis of asthma in children and adults with sickle cell disease (SCD) has been associated with increased rates of pain and acute chest syndrome (ACS) episodes and premature death. Despite the clinical significance of a doctor's diagnosis of asthma in individuals with SCD, the criteria for a physician diagnosis of asthma are not well defined. Many features of asthma are common in individuals with SCD, including symptoms of wheezing, obstructive lung disease and airway hyper-responsiveness. However, it is not clear if these signs and symptoms of asthma reflect a physician diagnosis of asthma, or if these asthma features are related to SCD. Further complicating the diagnosis of asthma in children with SCD is the significant overlap in clinical manifestations between an asthma exacerbation and an ACS episode. Evidence supporting the concept that asthma and SCD are separate co-morbid conditions includes a similar prevalence of asthma between children with SCD and those in the general population and the observation that asthma is inherited in a familial pattern in the families of children with SCD. In contrast, there is significant evidence that asthma-like features may be associated with SCD without a diagnosis of asthma, including a higher than expected prevalence of airway hyper-responsiveness and obstructive lung disease. Regardless of whether SCD and asthma are distinct or overlapping co-morbid conditions, we recommend a systematic and complete evaluation of asthma when the diagnosis is suspected or when patients have multiple episodes of pain or ACS.
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PMID:Asthma and sickle cell disease: two distinct diseases or part of the same process? 2000 81

Black widow spider envenomation is commonly reported to poison centers. Black widow spider envenomation produces a clinical syndrome, known as latrodectism, characterized by headache, nausea, vomiting, several muscle cramping and pain, joint stiffness, hypertension, and regional diaphoresis. Black widow spider antivenom (Merck & Co, Inc, West Point, PA USA) is an effective and relatively safe treatment option. There is 1 clear case of anaphylaxis secondary to black widow spider antivenom reported in the medical literature. Here, we report a case of anaphylaxis to antivenom. A 12-year-old boy presented to the emergency department (ED) with diffuse, severe pain 2 1/2 hours after being bitten by a black widow spider on the right lower extremity. In the ED, the patient failed analgesic therapy with fentanyl and was given black widow spider antivenom. Within 45 minutes, he exhibited signs and symptoms consistent with anaphylaxis, including wheezing, chest tightness, pruritus, and urticarial rash. The patient was given standard therapy for anaphylaxis, and all of his signs and symptoms (including the pain secondary to the black widow envenomation) resolved over 6 hours of observation. Leading experts agree that the use of antivenom is indicated in cases of severe envenomation not responsive to standard therapy. Despite concern that the antivenom is an equine-derived whole IgG and can precipitate early hypersensitivity reactions, there is only 1 other reported case of anaphylaxis to the antivenom in the medical literature.
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PMID:Anaphylaxis to black widow spider antivenom. 2164 Nov 65

Prior studies of asthma in children with sickle cell disease (SCD) were based on reports of a doctor-diagnosis of asthma with limited description of asthma features. Doctor-diagnoses of asthma may represent asthma or wheezing unrelated to asthma. Objectives of this study were to determine if asthma characteristics are present in adults with a doctor-diagnosis of asthma and/or wheezing, and to examine the relationship between doctor-diagnosis of asthma, wheezing and SCD morbidity. This was an observational cohort study of 114 adults with SCD who completed respiratory symptom questionnaires and had serum IgE measurements. A subset of 79 participants completed pulmonary function testing. Survival analysis was based on a mean prospective follow-up of 28 months and data were censored at the time of death or loss to follow-up. Adults reporting a doctor-diagnosis of asthma (N = 34) were more likely to have features of asthma including wheeze, eczema, family history of asthma, and an elevated IgE level (all P < 0.05). However, there was no difference in pain or ACS rate, lung function, or risk of death between adults with and without a doctor-diagnosis of asthma. In contrast, adults who reported recurrent, severe episodes of wheezing (N = 34), regardless of asthma, had twice the rates of pain and ACS, decreased lung function and increased risk of death compared with adults without recurrent, severe wheezing. Asthma features were not associated with recurrent, severe wheezing. Our data suggest that wheezing in SCD may occur independently of asthma and is a marker of disease severity.
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PMID:Recurrent, severe wheezing is associated with morbidity and mortality in adults with sickle cell disease. 2180 69


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