Discrepancy between clinical asthma control assessment tools and fractional exhaled nitric oxide.

BACKGROUND: Asthma is an inflammatory disease, yet clinical tools that evaluate asthma control do not include measures of inflammation. OBJECTIVE: To determine the correlation between fractional exhaled nitric oxide (FeNO) and each of 5 asthma control evaluation tools, namely, the Asthma Control Questionnaire (ACQ), the Asthma Control Test (ACT), the National Asthma Education and Prevention Program (NAEPP) goals of therapy, the Joint Task Force Practice Parameter (JTFPP) on attaining optimal asthma control, and the Global Initiative for Asthma (GINA) guidelines. METHODS: Patients 6 years or older who had asthma were clinically evaluated by an asthma specialist. Patients completed the ACT and ACQ and underwent spirometry and FeNO measurement. The physician was blinded to FeNO results until asthma control assessments were concluded. Correlations between FeNO level and each clinical evaluation tool were calculated. RESULTS: One hundred patients 6 to 86 years old were enrolled. No significant association was found between FeNO level and asthma control based on ACQ (P > .99), ACT (P = .53), NAEPP (P = .53), JTFPP (P = .30), or GINA (P = .86) criteria. Agreement was high among the NAEPP, the JTFPP, and GINA; moderate between the ACQ and the ACT; and poor to fair between the ACT or the ACQ and the other 3 tools. CONCLUSIONS: In addition to clinical evaluation, the incorporation of FeNO measurement in evaluating asthma is likely to lead to a more optimal pharmacotherapy, guidance in adjusting the dosage of anti-inflammatory agents, and positive long-term disease outcome.

New concepts in the management of adverse drug reactions.

Our understanding of drug reactions and their management has changed markedly in recent years with the development of several new concepts. Epidermal cell death seen in Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) may result from Fas-Fas ligand-mediated apoptosis. Intravenous immunoglobulin (IVIG) contains anti-Fas antibodies that can abrogate apoptosis. Most studies on IVIG in SJS and TEN reported improvement in arresting disease progression and reduction in time to healing. Furthermore, several studies have dispelled the myth of sulfonamide cross-reactivity. Immune-mediated reactions against antibacterial sulfonamides are directed against two unique side chains that non-antibacterial sulfonamides do not contain. Certain patients seem to have a genetic predisposition for "multiple drug sensitivities." Hence, they may react to several drugs that are not necessarily cross-reacting. Also, multiple studies have shown that IgE-mediated nonsteroidal anti-inflammatory drugs (NSAIDs) cross-reactivity is uncommon. Rather, it is cyclooxygenase (COX) 1 inhibition that results in pseudoallergic reactions to multiple NSAIDs. Several studies have indicated that selective COX-2 inhibitors can be safely administered in patients with aspirin-exacerbated respiratory disease and NSAID-induced cutaneous reactions, although their use has been curtailed by their cardiovascular side effects. Biological agents, such as infliximab, are being increasingly used for a variety of diseases and have caused adverse reactions in some patients. Studies differ as to whether concomitant immunosuppressive use with infliximab affects the development of drug-specific antibodies and infusion reactions. Successful desensitization protocols have been developed for reactions to some of these agents.

Pathogenesis and recent therapeutic trends in Stevens-Johnson syndrome and toxic epidermal necrolysis.

OBJECTIVE: To review the current pathophysiologic mechanisms and recent therapeutic trends in Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). DATA SOURCES: A MEDLINE search for SJS and TEN in combination with Fas, Fas ligand (FasL), cytotoxic T cells, intravenous immunoglobulin, and cyclosporine for articles published in English during 1966 to 2006. STUDY SELECTION: Information was derived from original research articles and reviews published in peer-reviewed journals. RESULTS: The hallmark of SJS and TEN is epidermal cell apoptosis, which may be mediated through keratinocyte Fas-FasL interaction or through cytotoxic T-cell release of perforin and granzyme B. Whereas systemic corticosteroid therapy showed contradictory results, intravenous immunoglobulin (IVIG) and cyclosporine have shown promising outcomes. IVIG contains anti-Fas antibodies that can abrogate apoptosis when preincubated with keratinocytes. Most studies on IVIG in SJS and TEN reported improvement in arresting disease progression and reduction in time to skin healing. Because of variations among studies, the findings cannot be optimally compared. In general, mortality varied from 0% to 12% in studies that supported the use of IVIG and 25% to 41.7% in those that did not demonstrate a beneficial effect. Cyclosporine inhibits CD8 activation and thus may reduce epidermal destruction. Relatively few case reports and 1 case series have been published regarding the use of cyclosporine in SJS and TEN. In general, cyclosporine was associated with a significant improvement in time to disease arrest and to complete reepithelization, with no reported fatalities. CONCLUSIONS: Both IVIG and cyclosporine have been associated with enhanced healing and better survival through inhibition of apoptosis. Multicenter, randomized, placebo-controlled trials using a standardized design are needed to validate these findings.

Inhalational mold toxicity: fact or fiction? A clinical review of 50 cases.

BACKGROUND: Three well-accepted mechanisms of mold-induced disease exist: allergy, infection, and oral toxicosis. Epidemiologic studies suggest a fourth category described as a transient aeroirritation effect. Toxic mold syndrome or inhalational toxicity continues to cause public concern despite a lack of scientific evidence that supports its existence. OBJECTIVES: To conduct a retrospective review of 50 cases of purported mold-induced toxic effects and identify unrecognized conditions that could explain presenting symptoms; to characterize a subgroup with a symptom complex suggestive of an aeroirritation-mediated mechanism and compare this group to other diagnostic categories, such as sick building syndrome and idiopathic chemical intolerance; and to discuss the evolution of toxic mold syndrome from a clinical perspective. METHODS: Eighty-two consecutive medical evaluations were analyzed of which 50 met inclusion criteria. These cases were critically reviewed and underwent data extraction of 23 variables, including demographic data, patient symptoms, laboratory, imaging, and pulmonary function test results, and an evaluation of medical diagnoses supported by medical record review, examination, and/or test results. RESULTS: Upper respiratory tract, lower respiratory tract, systemic, and neurocognitive symptoms were reported in 80%, 94%, 74%, and 84% of patients, respectively. Thirty patients had evidence of non-mold-related conditions that explained their presenting complaints. Two patients had evidence of allergy to mold allergens, whereas 1 patient exhibited mold-induced psychosis best described as toxic agoraphobia. Seventeen patients displayed a symptom complex that could be postulated to be caused by a transient mold-induced aeroirritation. CONCLUSION: The clinical presentation of patients with perceived mold-induced toxic effects is characterized by a disparate constellation of symptoms. Close scrutiny revealed a number of preexisting diagnoses that could plausibly explain presenting symptoms. The pathogenesis of aeroirritation implies completely transient symptoms linked to exposures at the incriminated site. Toxic mold syndrome represents the furtive evolution of aeroirritation from a transient to permanent symptom complex in patients with a psychogenic predisposition. In this respect, the core symptoms of toxic mold syndrome and their gradual transition to chronic symptoms related to nonspecific environmental fragrances and irritants appear to mimic what has been observed with other pseudodiagnostic categories, such as sick building syndrome and idiopathic chemical intolerance.

Psyllium-associated anaphylaxis and death: a case report and review of the literature.

BACKGROUND: Psyllium use has increased significantly in the United States in part due to its lipid-lowering property. The increased prevalence of consumption has led to its recognition as an emerging food allergen. OBJECTIVES: To report the case of a 42-year-old woman who experienced fatal anaphylaxis after ingesting a psyllium-based product and to review the literature. METHODS: The MEDLINE database was searched for articles from 1966 to 2002 using the keywords psyllium or ispaghula and each of the following: allergy, hypersensitivity, anaphylaxis, and asthma. Both English and non-English articles were included. RESULTS: Psyllium hypersensitivity has been well described in health care workers and pharmaceutical plant employees. Clinical manifestations of allergy range from upper respiratory tract symptoms on inhalation to anaphylaxis on ingestion. The prevalence of sensitization varies between these 2 groups. The allergenic epitope is not known. CONCLUSIONS: We present a case of psyllium hypersensitivity that resulted in death. There is a clear association between atopy and psyllium allergy. The case underscores the fact that even nonprescription "natural" products can be harmful to people with allergies.