Passive transfer of tuberculin reactivity in vitro.

A factor capable of effecting passive transfer in vivo of delayed hypersensitivity to tuberculin to recipients that are tuberculin negative was isolated from the dialyzate of disrupted leukocytes of tuberculin-positive individuals. After this factor was incubated with cultures of peripheral leukocytes from tuberculin-negative individuals, the addition of purified protein derivative of tubercle bacilli resulted in leukocyte stimulation similar to that observed after addition of purified protein derivative to leukocytes from tuberculin-positive individuals.

Development of IgE antibodies to human (recombinant DNA), porcine, and bovine insulins in diabetic subjects.

Thirty-one previously untreated diabetic individuals received only human insulin (recombinant DNA) for 1 yr with no adverse reactions. The development of serum IgE antibodies to human, porcine, and bovine insulins was assessed by a sepharose radioallergoabsorbent test (RAST). Immunoglobulin (total Ig antibody) binding was assessed by a nonabsorbed species-specific radioimmunoassay. During therapy 2 patients developed IgE antibodies to human insulin as well as increased total Ig binding. The IgE antibodies to human insulin cross-reacted with porcine and bovine insulins, were transient, and were not accompanied by insulin allergy. Ig binding to insulin developed and persisted in 11 of the human insulin-treated diabetics. In comparison, 62 previously untreated diabetic persons received only purified porcine insulin (PPI, less than 5 ppm proinsulin, N = 40) or a mixed bovine-porcine insulin (proinsulin less than 50 ppm, N = 21). Increased Ig antibody developed in 16 of 21 patients receiving mixed bovine-porcine insulin and 25 of 41 PPI-treated patients (P less than 0.05). Seven of 41 PPI-treated patients and 4 of 21 mixed bovine-porcine-treated patients developed anti-insulin IgE antibodies, which were transient in 4 and persisted in 6 diabetic patients. IgE antibody levels did not correlate with total Ig antibody. These data suggest that IgE and total Ig antibodies develop less often after human insulin treatment. Also, the immunoregulation mechanisms responsible for anti-insulin IgE antibody synthesis differ from those regulating other Ig that bind to insulins. Since none of the patients in this study have developed clinical manifestations of insulin allergy or resistance, the clinical relevance of the antibody data must remain speculative.

Prophylaxis of attacks of hereditary angioedema.

Danazol, an attentuated androgen, has been suggested as an effective agent for the prophylaxis of attacks of hereditary angioedema. Four patients, with a clinical history of hereditary angioedema and a demonstrated depression of the serum inhibitor of the first component of complement (C1 INH) and the fourth component of complement (C4), were entered into a study to determine the minimum effective dose of this agent. All four of the patients had been experiencing attacks at least monthly, but they had only six attacks during a total of 60 patient months of Danazol therapy. The minimum effective dose varied from 100 to 400 mg/day. The drug appeared to work by increasing the level of serum C1 INH which reached the normal range in two of four patients. Side effects were only the anticipated menstrual irregularities in the female patients. Danazol appears to be an efficacious drug for prophylaxis of hereditary angioedema.

Teaching self-management skills to asthmatic children and their parents in an ambulatory care setting.

A program designed to teach self-management skills to asthmatic children and their parents was performed by a nurse-educator utilizing health education techniques. Goals included: (1) reduce frequency and severity of asthma; (2) reduce emergency room visits and hospitalizations; (3) reduce school absenteeism; (4) develop positive family self-help attitudes; and (5) incorporate patient-parent education in an office. After informed consent was obtained, 26 asthmatic children, aged 2 to 14 years, were selected and evaluated. Appropriate asthma management including avoidance, medications, and immunotherapy, if indicated, was initiated for both a study group (13 patients) and a comparison group (13 patients). Symptom and medication diaries were kept for six to 18 months. Educational intervention by a nurse-educator, including four hours of individual instruction, group classes, telephone access, and monitoring for the study patients, resulted in fewer hospitalizations and emergency room visits as compared to control patients, tenfold less school absenteeism, and fewer asthma attacks. Estimated hospital and emergency room costs were much less in the educated group. These results were accomplished by improving comprehension of and compliance with the medical management program by the study patients and their families; more medications were used and therapy for asthma was initiated earlier.

Perception of expiratory flow by asthmatics and non-asthmatics during rest and exercise.

Perception of respiratory function may be an important factor in self-management of asthma. Previous research has suggested that asthmatics may not accurately perceive pulmonary functioning. The perception of normal and asthmatic individuals was assessed using a magnitude production procedure in a series of three studies, proceeding from normal individuals during rest, then submaximal exercise, to a comparison of normal and asthmatic adolescents during rest and submaximal exercise. At rest there were no differences between males and females, adults and adolescents, or asthmatics and non-asthmatics. However, there were significant differences in perception between rest and exercise for all groups. These findings suggest that a breakdown in perception does not occur during submaximal exercise in patients with asthma.

Sinusitis and asthma: clinical and pathogenetic relationships.

Sinusitis has been considered to be a possible causal factor for asthma. Reflex has also been postulated between the upper and lower airway. Data for and against the existence of such a reflex are presented, together with the diagnosis and management of sinusitis.

Pathophysiology and pharmacotherapy of common upper respiratory diseases.

The response of the upper respiratory tract to many environmental factors can be used both to analyze the body's inflammatory process and to choose appropriate therapy. The nose is the major pathway to the lungs, upper airways, sinuses, middle ears, and other parts of the body, and its reactions often represent a major portion of the problem. The most common upper respiratory illnesses are upper respiratory infections (URIs), primarily viral, followed by secondary bacterial infections. Approximately 20% of the total population may manifest allergic rhinitis, which is mediated by immunoglobulin E. This condition is often referred to as hay fever, although there is no direct allergy to hay, and there is no fever. The differential diagnosis includes nonallergic rhinitis with eosinophils, which mimics the pathophysiology of allergic rhinitis but yields negative results on skin testing; vasomotor and hormonal rhinitis; and rhinitis medicamentosa, the rebound congestion associated with overuse of topical adrenergic agents. Therapeutic options include avoiding causative agents, immunotherapy, and pharmacotherapy. Antihistamines produce excellent results in allergic rhinitis when sneezing and itching are present, but are of minimal value as decongestants. The alpha-adrenergic agonists are the optimum choices for congestion associated with viral URIs, and allergic or nonallergic rhinitis. Of major importance are accurate diagnosis, selection of appropriate therapy, and patient compliance.

State and trait negative affect as predictors of objective and subjective symptoms of respiratory viral infections.

State and trait negative affect (NA) were measured in healthy people immediately before an illness was induced through exposure to a respiratory virus. State NA, disease-specific health complaints (e.g., runny nose, congestion, and sneezing), and an associated objective marker of disease severity (mucus secretion weights) were assessed daily during the illness. Baseline trait and state NA were both associated with increased numbers of subsequent complaints. Although greater numbers of complaints among people high in state NA were explicable in terms of greater disease severity, the association of trait NA and symptoms was independent of objective disease. The trait NA complaint association was also independent of state NA and hence not attributable to trait-elicited state affect. Greater trait NA was associated with biases in complaining during but not before illness. This suggested failure to discriminate between symptoms rather than increased sensitivity or hypochondriacal response.

Otologic manifestations of experimental rhinovirus infection.

Episodes of acute otitis media are commonly associated with viral upper respiratory tract infections. Rhinoviruses account for approximately 40% of these infections, and were previously shown to alter eustachian tube function and middle ear pressures. However, progression to otitis media has not been prospectively documented. In the present study, changes in tympanometric pressures and otoscopic findings resulting from experimental intranasal rhinovirus type-39 inoculation were documented in 60 adult volunteers. Fifty-seven (95%) subjects became infected and 34 (60%) of these had a clinical cold. Prior to viral inoculation, 3 (5%) subjects had middle ear pressures of less than -100 mm H2O and two of these subjects developed middle ear effusions following infection. In all, 22 (39%) subjects developed middle ear pressures of less than -100 mm H2O. No subject with normal middle ear pressures prior to infection developed evidence of effusion. This study extends the otologic manifestations of rhinovirus infection to include otitis media. Furthermore, these results support the hypothesized relationship between upper respiratory tract infections, eustachian tube dysfunction, and otitis media.

Eustachian tube obstruction after intranasal challenge with house dust mite.

Past studies have shown that provocative intranasal pollen challenge in allergic subjects results in signs and symptoms of allergic rhinitis, nasal obstruction, and eustachian tube obstruction. The study presented herein extends these observations to challenges with a perennial antigen, house dust mite. Twenty-three adult volunteers with confirmed sensitivity to Dermatophagoides farinae were challenged by intranasal inhalation of antigen in doses that were incremented from 0.5 to 10.0 mg. Eustachian tube function by the nine-step pressure-swallow test and nasal airway resistance by anterior rhinomanometry were evaluated before and after challenge. Twenty-two of the 40 ears showing normal tubal function before challenge were abnormal after challenge. Sixteen of the 23 subjects developed a nasal obstruction after challenge. The median specific serum IgE antibody titer for those individuals responding to the challenge was significantly greater than that of the individuals exhibiting no response. These results show that intranasal challenge with D farinae can provoke immune-mediated nasal obstruction and eustachian tube dysfunction in sensitized subjects.

Inflammatory mediators in chronic otitis media with effusion.

Otitis media with effusion (OME) is a common middle ear inflammatory disease in the pediatric population. This article determines concentrations of three functionally and metabolically distinct inflammatory mediators in middle ear effusions (MEE) and corresponding plasma of children with OME. One hundred two patients (mean age, 4.9 years) with persistent OME were studied. Middle ear effusions were collected from all subjects and plasma from a subset at the time of tympanostomy tube insertion. Histamine was assayed radioisotopically, 13,14-dihydro-15-keto-prostaglandin F2 alpha (stable PGF2 alpha metabolite) by radioimmunoassay, and neutrophil chemotactic factor of anaphylaxis by modified Boyden chamber. Mean MEE levels of the mediators (39 +/- 13 ng/mL, 462 +/- 179 pg/mL, and 264% +/- 57% positive control, respectively) were markedly higher than those of corresponding plasma (0.5 +/- 0.1 ng/mL, 285 +/- 127 pg/mL, and 47% +/- 5% positive control, respectively). The mean histamine content of mucoid effusions (43.2 +/- 56.9 ng/mL) was significantly higher than that of purulent (22.5 +/- 10.5 ng/mL) and serous (17.9 +/- 16.8 ng/mL) effusions. Higher histamine levels were observed in effusions positive for Haemophilus influenzae when compared with those with other pathogenic isolates. The high concentrations of these mediators in MEE and their potential for inducing or sustaining the inflammatory process supports a role in the pathogenesis of OME.

Cytokines, immunoglobulins, and bacterial pathogens in middle ear effusions.

OBJECTIVE: To elucidate the role of cytokines, immunoglobulins, and bacterial pathogens in the middle ear effusions (MEEs) of children with otitis media (OM). DESIGN: Paired MEEs and serum samples collected from consecutive patients were assayed for immunoglobulins. Middle ear effusions were cultured for bacterial pathogens and assayed for interleukin-1 beta, interleukin-6, tumor necrosis factor alpha, and interferon gamma. The medical charts of the patients were retrospectively reviewed to define the history of OM. SUBJECTS: Seventy-five patients with a history of recurrent acute OM, persistent OM with effusion, or both. Exclusion criteria included the presence of a major coexisting condition, or an unclear or atypical history of OM. SETTING: A private practice at a tertiary care children's hospital. INTERVENTIONS: At the time of tympanostomy tube placement, with the patient under general anesthesia, one MEE and a serum sample were collected. RESULTS: Interleukin-1 beta was detected in 58% (44/75) MEEs; interleukin-6, 83% (60/72); tumor necrosis factor alpha, 37% (28/75) [corrected]; and interferon gamma, 61% (45/74). Concentrations of interleukin-1 beta, interleukin-6 and tumor necrosis factor alpha in MEEs were highly correlated with each other (P < .01 for each association) suggesting increased local production and the expected effects of cytokines stimulating their own production during OM. High concentrations of tumor necrosis factor alpha in MEEs were also associated with a history of multiple placements of tympanostomy tubes (r = .63). CONCLUSIONS: These data suggest a regulatory role for cytokines in inflammation during OM, and suggest that high concentrations of tumor necrosis factor alpha in MEEs may be a marker for OM chronicity.

Otitis media and its relationship to allergy.

The importance of infection in the etiology of otitis media and the role of eustachian tube obstruction in the pathogenesis of otitis media with effusion are well known. Recently, allergic rhinitis has been documented to induce eustachian tube obstruction. When allergic rhinitis is diagnosed in a child with recurrent or chronic middle ear disease, allergy should be considered as another risk factor for the development of otitis media with effusion.

Morbidity and mortality of asthma.

Morbidity and mortality of asthma has been on the upswing since the 1960s, as marked by increased hospitalizations with asthma since the early 1980s. This has not been explained adequately. The possibility of change in the natural history or increased exposure to environmental irritant chemicals or allergens has been suggested by some. There probably has been better recognition and diagnosis of asthma by distinguishing it from bronchitis, recurrent croup, and bronchiolitis in children. Despite evidence to suggest that this is the case, there are still some missing factors. The increase in asthma mortality is more understandable when one considers the fact the management of asthma has changed greatly in the past two decades. The use of corticosteroids orally, parenterally, and by inhalation has been a double-edged sword. There is no doubt that many asthmatics have a much improved sense of well-being and have lived more normal lives due to the use of corticosteroids. The inability of some patients, parents, or physicians to perceive impending respiratory difficulty, however, may result in underuse of drugs, including corticosteroids, leading to increased mortality. Other factors have led to increased mortality from asthma in recent years, and they include arrhythmias with combinations of theophylline, beta-agonists, and hypoxia. The psychological factors attendant to adolescence and psychological problems are probably quite important in the recent upsurge in asthma deaths in the 15- to 25-year age group. Many deaths are occurring outside of the hospital environment and may be largely preventable. There must be increased awareness by the patient, the family, and the physician. In view of the increased hospitalizations, the total number of deaths is not increasing at an alarming rate, yet it is necessary to make all of us who care for asthmatics aware and take corrective action as soon as we are aware of an asthmatic with respiratory problems.

Sinusitis: bench to bedside. Current findings, future directions.

Sinusitis, an inflammatory disease of the sinus, is one of the most commonly reported diseases in the United States, affecting an estimated 14% of the population. The prevalence of sinusitis is rising. Between 1990 and 1992, persons with sinusitis reported approximately 73 million restricted activity days--an increase from the 50 million restricted activity days reported between 1986 and 1988. Because critical questions remain unanswered about its cause, pathophysiology, and optimal treatment, sinusitis continues to generate significant health care costs and affects the quality of life of a large segment of the U.S. population. To identify critical directions for research on sinus disease, the American Academy of Allergy, Asthma and Immunology and the American Academy of Otolaryngology-Head and Neck Surgery Foundation, Inc., convened a meeting in January 1996 in collaboration with the National Institutes of Allergy and Infectious Disease. This document summarizes the proceedings of that meeting and presents what is intended to be the background for future investigation of the many unanswered questions related to sinusitis.

Neuropsychological functioning in children with immunodeficiency disorders.

A small group of children with various types of immunodeficiency disorders, examined on a battery of neuropsychological and intellectual tests, was found to be impaired on perceptual speed, visuospatial sequencing, and visual attention span capacities when compared to a control group of closest aged siblings and normal children matched for age, education, and IQ. The results suggest that cerebral dysfunction may be associated with immunodeficiency disorders in children, although these findings are tentative since other factors, such as the effects of chronic illness, could not be excluded in this small cohort of patients.

Nasal and otologic effects of experimental influenza A virus infection.

Past studies showed that experimental rhinovirus colds in adults resulted in eustachian tube dysfunction and abnormal middle ear pressures. In the present study, the symptoms and pathophysiologic findings accompanying experimental influenza viral infection were documented. A total of 33 healthy adult volunteers were intranasally challenged with an influenza A/Kawasaki/86 (H1N1) virus and cloistered over a 9-day postchallenge period to monitor for evidence of infection, signs and symptoms of illness, and the extent and frequency of pathophysiologic responses of the nose, eustachian tube, and middle ear. Results showed a protective effect of high (> or = 16) prechallenge specific hemagglutination-inhibition antibody titer on the rate of infection and the magnitude and extent of provoked symptoms and pathophysiologic findings. Infected subjects with low (< 16) prechallenge serum antibody titers (n = 21) developed significant respiratory illness. These subjects also had objectively measurable increases in nasal secretion production, and decreased nasal patency and mucociliary clearance rates. More than 80% of the infected subjects developed eustachian tube dysfunction, and approximately 80% had middle ear underpressures of less than -100 mm H2O on study days 4 and 5. Five of 21 infected subjects with low prechallenge antibody titers had otoscopic evidence of otitis media with effusion. These results support a causal role for viral upper respiratory tract infection in the pathogenesis of otitis media, possibly mediated by the early development of eustachian tube dysfunction and abnormal middle ear pressure.

Suppression of in vivo cell-mediated immunity during experimental influenza A virus infection of adults.

A variety of recent evidence documents that otitis media is a frequent complication of upper respiratory tract viral infections. This relationship has been attributed to the interaction of a number of virus-provoked host responses, including eustachian tube dysfunction, changes in nasopharyngeal bacterial flora and suppressed immune function. The present study examined the effect of experimental influenza A virus infection on immune function as assessed by delayed skin test reactivity to candida, tetanus, and diphtheria/tetanus antigens in healthy adults with (n = 12) and without (n = 15) allergic rhinitis. All subjects became infected with the challenge virus as evidenced by viral shedding into nasal secretions and/or a four-fold rise in convalescent serum antibody titers compared to baseline. Intradermal skin tests were placed at baseline and 2, 4, 17, and 24 days after intranasal influenza A inoculation, the reactions were imaged and recorded 48 h after placement, and response areas were calculated by computerized digitization. The average combined areas for the three antigens (+/- S.T.D.) on each of the 5 study days were 1.4 +/- 1.4, 0.7 +/- 0.7, 0.6 +/- 0.6, 1.4 +/- 1.4, and 1.2 +/- 1.2 cm2, respectively. The responses to candida, but not tetanus and diphtheria/tetanus, returned to baseline levels by day 17. Repeated measures ANOVA documented significant effects of study day and antigen, but not allergy status. These results show that experimental influenza A infection suppressed delayed hypersensitivity skin tests in both allergic and non-allergic subjects, and suggest that alterations in immune function may contribute to otitis media.

Body odor in dermatologic diagnosis.

Patients with an unpleasant body odor often consult dermatologists. A dermatologist needs to become familiar with the occurrence and significance of medically related odors. Although body odor may be essentially physiological, and problems with body mal-odor are paid little attention, they can cause many personal troubles and may induce a variety of psychosocial disturbances. Body odor in general is an indicator of individual care and hygiene, or results from eating garlic, onion, spicy foods, curry, or drinking alcohol; however, in some instances it can be pathologic. It is a well-known clinical fact that many diseases (both of internal and cutaneous origin), several syndromes, and some intoxications cause characteristic, peculiar, and identifiable odors. Their identification can provide diagnostic clues, guide the laboratory evaluation, and help in the choice of immediate and appropriate therapy. Thus, olfactory evaluation can be an important part of clinical examination and olfactory diagnosis is still valid in recognizing certain diseases. This report reviews the physiological and pathologic body odors and the importance of olfactory diagnosis in dermatology.

Pattern of nasal secretions during experimental influenza virus infection.

To define the pattern of secretion production during influenza virus infection, 28 adult subjects were inoculated with influenza-A virus (H1N1) and cloistered for a period of 8 days. On each day, symptoms associated with virus infection were scored, nasal secretions were collected and nasal lavages were performed. Recovered lavage fluids were submitted for virus culture and assayed for proteins, histamine, and bradykinin. Twenty-one subjects were infected with influenza-A virus and had significant increases in daily secretion weights and symptom scores extending from day 2 to 7, post-inoculation. Plasma-derived proteins in the nasal lavage fluids showed an early increase to peak at day 4 and then decreased. Glandular proteins showed a later increase to peak at day 5. Bradykinin but not histamine was significantly elevated and tracked the changes in the glandular proteins. In contrast, a shallow increase in symptoms confined to day 2 post-inoculation, but no increase in daily secretion weights was documented in the seven uninfected subjects. There, an increase in plasma proteins was observed on days 1 and 2, but no change in glandular proteins was obvious. These results support a biphasic secretory response during influenza-virus infection with transudation dominating the early period and glandular secretions contributing later.