Nasal lavage microbiome, but not nasal swab microbiome, correlates with sinonasal inflammation in children with cystic fibrosis.

BACKGROUND: Cystic fibrosis (CF) is characterized by highly viscous mucus obstructing the lower and upper airways, chronic neutrophil inflammation and infection resulting not only in lung destruction but also in paranasal sinus involvement. The pathogenesis of CF-associated chronic rhinosinusitis (CRS) is still not well understood, and it remains unclear how the microbiome in the upper airways (UAW) influences paranasal sinus inflammation. METHODS: In a cross-sectional study in pediatric patients with CF under stable disease conditions, we examined the microbiome in relation to inflammation by comparing nasal swabs (NS) and nasal lavage (NL) as two UAW sampling methods. The microbiota structure of both NS and NL was determined by 16S rRNA gene amplicon sequencing. In addition, pro-inflammatory cytokines (IL-1ß, IL-6, IL-8, TNF-α) and proteases (SLPI, TIMP-1, NE/A1-AT complex) as well as neutrophil elastase activity were measured in NL. RESULTS: Simultaneous NS and NL samples were collected from 36 patients with CF (age range: 7 - 19 years). The microbiome of NS samples was shown to be significantly lower in α-diversity and evenness compared to NL samples. NS samples were particularly found to be colonized with Staphylococcus species. NL microbiome was shown to correlate much better with the sinonasal inflammation status than NS microbiome. Especially the detection of Moraxella in NL was associated with increased inflammatory response. CONCLUSION: Our results show that the NL microbiome reflects sinonasal inflammation better than NS and support NL as a promising tool for simultaneous assessment of the UAW microbiome and inflammation in children with CF.

Metagenome - Inferred bacterial replication rates in cystic fibrosis airways.

Bacterial replication rates were determined from metagenome sequencing of nasal lavage, throat swabs and induced sputa collected from healthy subjects and individuals with COPD or cystic fibrosis. More than 90% of peak-to-trough coverage ratios of major clones were above 1.4 indicating that the most abundant bacterial species in the microbial communities were replicating in the airways including common inhabitants such as Prevotella and Streptococcus species as well as the cystic fibrosis pathogens Staphylococcus aureus and Pseudomonas aeruginosa. The populations of P. aeruginosa and S. aureus were replicating their pool of chromosomes more slowly than the populations of the common inhabitants of a healthy airway microbial flora. The assessment of growth dynamics in microbial metagenomes could become a decision-making tool for the diagnosis and management of bacterial infections in cystic fibrosis.

The burden of sinus disease in cystic fibrosis lung transplant recipients.

INTRODUCTION: Sinus disease (SD) in cystic fibrosis (CF) is a known risk factor for disease progression, the upper airways (UAW) being a site of primary colonization with Pseudomonas aeruginosa. UAW may function as reservoir for graft colonization after lung transplantation (LuTx), increasing risk of rejection. Aims of this study were to assess the burden of sinus disease in CF LuTx recipients, considering patient-reported symptoms, endoscopically documented signs and microbiological isolates, comparing colonization between upper and lower airways. METHODS: A prospective, observational study was performed on consecutive CF LuTx recipients, recording history, symptoms, and management of SD. Nasal lavage (NL) was evaluated for UAW colonization, with nasal inspection during bronchoscopy and bronchoalveolar lavage (BAL) used to assess lower airways if clinically indicated. RESULTS: Hundred and fifty-four patients were included. Symptoms of SD were reported in 96 (62%) individuals; 87 (56%) had prior sinus surgery. Only 8 (13%) of 60 individuals undergoing bronchoscopy presented completely normal findings of the nasal cavity. Thirty-six (60%) patients presented the same isolates on both NL and BAL. Polyps and mucosal alterations were significantly less frequently seen endoscopically in patients with normal flora in NL microbiology (respectively, 26% vs 70%, P = .003, and 35% vs 68%, P = .013). CONCLUSIONS: Symptoms of SD affected more than 60% of CF LuTx recipients. Nasal endoscopic inspection identified alterations in 55%. The majority of patients presented the same isolates both on NL and BAL performed on the same visit. These results strongly support a role of paranasal sinuses as "reservoir" for descending re-colonization of the lung graft.

Performance of the cobas MRSA/SA Test for Simultaneous Detection of Methicillin-Susceptible and Methicillin-Resistant Staphylococcus aureus From Nasal Swabs.

OBJECTIVES: Health care-associated methicillin-resistant Staphylococcus aureus (MRSA) and Staphylococcus aureus (SA) infections are continuing problems. Rapidly determining the MRSA colonization status of a patient facilitates practice to reduce spread of MRSA clinical disease. Sensitive detection of all SA prior to surgery, followed by decolonization, can significantly reduce postoperative infection from this pathogen. Our goal was to validate a new automated assay for this testing. METHODS: We compared performance of the cobas MRSA/SA Test on the cobas 4800 System to direct and enriched chromogenic culture using nasal swabs collected from patients at six United States sites. RESULTS: Compared to direct and enriched culture, the sensitivity for MRSA and SA was 93.1% and 93.9%, and the specificity was 97.5% and 94.2%, respectively. After discrepancy analysis, the sensitivity for MRSA and SA was 97.1% and 98.6%, and the specificity was 98.3% and 95.5%, respectively. Compared to direct culture, sensitivity for detecting any SA was 99.6%. CONCLUSIONS: The cobas MRSA/SA Test is an effective tool to simultaneously perform surveillance testing for nasal colonization of both MRSA and MSSA.

Chronic illness associated with mold and mycotoxins: is naso-sinus fungal biofilm the culprit?

It has recently been demonstrated that patients who develop chronic illness after prior exposure to water damaged buildings (WDB) and mold have the presence of mycotoxins, which can be detected in the urine. We hypothesized that the mold may be harbored internally and continue to release and/or produce mycotoxins which contribute to ongoing chronic illness. The sinuses are the most likely candidate as a site for the internal mold and mycotoxin production. In this paper, we review the literature supporting this concept.

Microwave disinfection: assessing the risks of irrigation bottle and fluid contamination.

BACKGROUND: It was previously shown that 50% of irrigation bottles and 40% of irrigation fluids had evidence of bacterial contamination despite cleaning with hot water and soap. Although a novel method of microwave disinfection has recently been proposed to minimize contamination risk, this has not been studied in a real life setting. This study investigates the effectiveness of microwave disinfection for reducing both nasal irrigation bottle and irrigation fluid contamination risk after endoscopic sinus surgery (ESS). METHODS: Twenty consecutive patients underwent ESS for chronic rhinosinusitis. Patients were given NeilMed Sinus Rinse bottles (NeilMed Pharmaceuticals, Inc., Santa Rosa CA) to use twice daily, with microwave cleaning instructions preoperatively. Bottles were collected and cultured 1 week postoperatively. Sterile saline (5 mL) was mixed into the irrigation bottle and cultured separately. An additional 10 patients were recruited whereby the bottle was cultured at collection and immediately after microwave disinfection was performed in the clinic. RESULTS: For the first cohort of the study, 40% of the bottles and 20% of the irrigation samples had positive cultures 1 week postoperatively. Common bacteria included Acinetobacter, coagulase-negative Staphylococcus, and Gram-negative bacilli. For the second cohort of patients, 20% of the irrigation bottles had positive cultures. However, after supervised microwave disinfection, there was a 0% contamination rate. CONCLUSION: Despite detailed instructions on microwave disinfection, positive bacterial cultures may still occur after ESS. This risk, however, appears to be significantly reduced when bottles are microwaved under supervision. These findings suggest either a reduced patient compliance to cleaning or a time-dependent recontamination risk after disinfection.

Microbiological outcomes following mupirocin nasal washes for symptomatic, Staphylococcus aureus-positive chronic rhinosinusitis following endoscopic sinus surgery.

BACKGROUND: Persistent infection following endoscopic sinus surgery (ESS) for chronic rhinosinusitis (CRS) is a frustrating entity for the patient and rhinologist alike. Mupirocin nasal washes have been proposed as an efficacious treatment in such patients. Two small studies have reported excellent short-term posttreatment outcomes; however, the long-term microbiological outcomes following treatment are not known; likewise, the rate of mupirocin-resistance following treatment has not been explored. METHODS: This was a retrospective chart review of 61 patients with Staphylococcus aureus (S. aureus)-positive surgically-recalcitrant CRS having undergone 0.05% mupirocin nasal rinse treatment, twice daily for 4 weeks. Specific outcomes reported included posttreatment culture results, time to first posttreatment S. aureus culture, and mupirocin-sensitivity following treatment. RESULTS: Of 57 patients meeting minimal posttreatment follow-up criteria, 42 (73.7%) progressed to microbiological failure by subsequently cultured S. aureus. Mean time to first positive culture was 144 days. Of the 42 patients who progressed to microbiological relapse, full antibiotic sensitivity data was available for 41; of these, only 1 was found to subsequently harbor a mupirocin-resistant strain of S. aureus, thus yielding a posttreatment resistance rate of 2.4%. CONCLUSION: Treatment with mupirocin nasal washes in S. aureus-positive, surgically recalcitrant CRS has a high microbiological failure rate, with 73.7% of patients subsequently re-culturing S. aureus. Our current treatment regime of 0.05% nasal washes twice daily for 4 weeks is associated with a posttreatment resistance rate that is consistent with other studies of topical mupirocin use, suggesting that mupirocin washes are no more likely to induce resistance than nasal vestibule decolonization in the high-risk medical or surgical patient.

Developing a mouse model of acute bacterial rhinosinusitis.

The objective of this study is to establish a mouse model of acute bacterial rhinosinusitis. 179 healthy male BALB/c mice were divided into four groups in this randomized and controlled study. Sponge slivers impregnated with methicillin-resistant Staphylococcus aureus (MRSA COL) suspension were inserted into the right nasal cavities for group A; sponge slivers impregnated with sterile saline were inserted into the right nasal cavities for group B; group C mice were inoculated with MRSA COL suspension in right nasal cavities; group D was control group without any treatment. Mice were killed on days 1, 4, 7 and 14, respectively. Nasal lavage fluid was prepared for microbiological culture. Histological examinations of nasal specimens were performed to observe the severity of inflammatory reaction. Acute bacterial rhinosinusitis was induced in all group A mice. Less severe inflammation was seen in partial group B mice compared with that in group A mice (P ≤ 0.05). No inflammatory reaction was found in group C and D mice. In conclusion, a mouse model of acute bacterial rhinosinusitis has been developed successfully using an easier, less invasive and potentially more reversible technique than those used in previous studies.

Rhinosinusitis in COPD: symptoms, mucosal changes, nasal lavage cells and eicosanoids.

The coexistence of upper airways disease with chronic obstructive pulmonary disease (COPD) is not well documented. The aim of this research was to assess sino-nasal inflammation in COPD by various tools, and look for the impact on quality of life, relation to smoking, disease severity and systemic inflammation. Current and ex-smokers with COPD (n = 42) and healthy never-smokers (n = 21) were included in this study. COPD severity was assessed by GOLD criteria and BODE index. Markers of systemic inflammation were measured. Nasal symptoms and general quality of life were assessed using the questionnaires; sino-nasal questionnaire (SNAQ-11) and St. George's Respiratory Questionnaire (SGRQ). Nasal endoscopy and saccharine test were performed. Nasal lavages were collected for cytological examination and eicosanoids (cysteinyl leukotrienes, leukotriene B4, 8-isoprostane). Symptoms and endoscopic scores were higher in COPD (P < or = 0.0001). Only SGRQ symptoms subscore correlated with SNAQ-11 (r = 0.34, P = 0.035). Mucociliary clearance was impaired only in current smokers (9.91 +/- 0.49 versus 13.12 +/- 0.68 minutes, P < or = 0.001). 8-isoprostane was higher in COPD smokers compared to the controls (0.17 +/- 0.04 versus 0.34 +/- 0.09 pg/g protein, P < 0.05). Endoscopic score and mucociliary of impairment patients who currently smoked cigarettes correlated with concentrations of 8-isoprostane. None of the parameters correlated with disease severity and markers of systemic inflammation. We provide evidence of upper airways disease in COPD, which appears to be related more to patients who currently smoke than to disease severity.

Staphylococcus aureus in nasal lavage and biopsy of patients with chronic rhinosinusitis.

BACKGROUND: Staphylococcus aureus may play a relevant etiologic role in chronic rhinosinusitis (CRS) and may explain the T(H2) shift observed in CRS with nasal polyps (CRSNP(+)). Naturally occurring S. aureus small colony variants (SASCV) escape immune surveillance, antibiotic treatment and microbiologic routine diagnostic techniques. The frequency of S. aureus and SASCV in CRS patients and S. aureus-related effects on the local immune response should be prospectively investigated. METHODS: Nasal lavages and mucosal biopsies of CRS patients were examined with bacterial culture suitable for detecting SASCV, real time PCR and fluorescence in situ hybridization. To assess the effects of S. aureus positivity, interleukin-5 (IL-5), interferon-gamma, total immunoglobulin E (IgE), eotaxin, granulocyte-colony stimulating factor, and eosinophil cationic protein in nasal lavages were determined and gene transcription analysis of nasal biopsies from S. aureus positive and negative CRSNP(+) patients was performed. RESULTS: Thirty-one CRSNP(+) patients, 13 CRS patients without polyps, and 21 control patients were evaluated. Staphylococcus aureus was detected by any method in 25 patients (39%). Staphylococcus aureus detection rates did not differ between the three disease groups (P = 0.3). Staphylococcus aureus small colony variants were not found. In nasal lavages, IL-5 and total IgE levels were higher in CRSNP(+) patients than in CRSNP(-) patients or controls (P < 0.05). Staphylococcus aureus positivity did not influence biomarker concentrations in nasal lavages. Genes for T(H2) cytokines were not differentially transcribed. CONCLUSIONS: We could not observe a higher prevalence of S. aureus in CRS patients with or without nasal polyps than in controls. We could not substantiate that S. aureus intensifies the T(H2) shift in CRSNP(+) patients. Staphylococcus aureus small colony variants were not detected in any sample.

Effect of montelukast on bacterial sinusitis in allergic mice.

BACKGROUND: In mice, allergic rhinitis augments the infectious and inflammatory response to Streptococcus pneumoniae-induced sinusitis. OBJECTIVE: To investigate the effects of cysteinyl leukotriene antagonism on the severity of bacterial infection. METHODS: We performed 3 parallel, placebo-controlled experiments. In the first, mice were ovalbumin sensitized and ovalbumin challenged to show the effects of montelukast on the allergic inflammation; in the second, we evaluated the effect of montelukast on S. pneumoniae infection; in the third, we used mice that were both allergic and infected. Montelukast was given starting 2 days after sensitization until the day before euthanasia. One day after drug treatment began, the mice were inoculated intranasally with S. pneumoniae in the infected groups. Nasal hypersensitivity was measured with histamine challenges before the first sensitization and on the day before euthanasia. On the fifth day after infection, mice were euthanized, nasal lavage was performed, bacteria were cultured, and inflammatory cells in the sinuses were quantified. RESULTS: Mice that were infected only tended toward having increased bacterial counts from nasal lavage in the montelukast-treated group. The mice that were allergic and infected experienced significantly higher bacterial counts (P < .05). All 3 montelukast treatment groups had significantly decreased eosinophil counts as well as T-lymphocyte counts. CONCLUSIONS: Montelukast reduces the manifestations of allergic rhinitis in mice. Surprisingly, montelukast led to an increase in bacterial growth in infected mice. This suggests an effect of the cysteinyl leukotrienes on the innate response to bacterial infection.

Aspergillus fumigatus challenge increases cytokine levels in nasal lavage fluid.

Several studies have shown an association between exposure in moisture-damaged buildings and adverse health effects. There are several indicator microbes of moisture damage, but Aspergillus fumigatus is one of the best-documented molds provoking health problems in different occupational conditions. We assessed whether inhalation of a commercial A. fumigatus solution would affect cytokine levels (tumor necrosis factor [TNF]-alpha, interleukin [IL]-1beta, IL-4, IL-6, interferon [IFN]-gamma) in nasal lavage fluid (NAL) compared with that evoked by placebo challenge. Twenty-seven subjects were studied: 13 had occupational exposure in a moisture-damaged building, 4 were atopic, and 10 were considered as controls. In all the subjects, the IL-1beta levels were increased significantly both at 6 (p = 0.013) and 24 h (p = .005) after the A. fumigatus challenge compared to placebo. In subjects with previous occupational exposure in a moisture-damaged building, IL-4 concentrations were increased significantly both at 6 (p =.046) and 24 h (p =.008) after the A. fumigatus challenge compared with placebo. Furthermore, in the control group, TNF-alpha levels were significantly increased at 6 h after the A. fumigatus challenge compared to placebo (p = .028). Thus, these data show a link between markers of inflammation in NAL and experimental A. fumigatus challenge.

Fungal cultures of different parts of the upper and lower airways in chronic rhinosinusitis.

The relation between fungi, upper and lower airways in chronic rhinosinusitis (CRS) patients are not clear yet. So the aim of this study was to identify the different cultured fungi in various sub-sites of the nasal cavity and lower airways in adult (CRS) patients and to correlate the cultured fungi to the associated cellular inflammatory changes. In the outpatient clinic a control group of 10 normal subjects was subjected to total nasal lavages to validate our mycological culture technique. Twenty-five adult CRS patients were enrolled in this prospective study. Under general anaesthesia before functional endoscopic sinus surgery (FESS) operation 50 nasal vestibular swabs, 25 bronchoalveolar lavages (BALs), 50 middle meatal lavages (MMLs) and 50 nasal cavity lavages (NCLs) were obtained in the operating room. These samples were processed for fungal culture and eosinophilic cellular counts. The intraoperative pathological specimens were examined using Haematoxylin and Eosin (H&E) and Gomori methanamine silver (GMS) staining. In the normal control group total nasal lavages showed 100% positive fungal cultures. In the CRS patient group the BALs showed positive fungal cultures in 28%. Nasal vestibule cultures were positive in 8%. Positive middle meatal cultures were obtained in 44% of the 25 CRS patients. Two cases (8%) with maxillary fungal ball showed a positive maxillary sinus culture but a negative middle meatal culture. Nasal cavity lavages were positive in 36%. Middle meatal eosinophilia was identified in 33.6% of the positive middle meatal fungal culture. Following the deShazo's criteria of diagnosis of allergic fungal rhinosinusits (AFRS), only 16% of the subjects in this study fulfilled the criteria. No correlation existed between fungal culture, cellular and other clinical parameters. Also no correlation existed between upper and lower airway positive cultures. In conclusion fungi seemed to be present in different percentages and types in different sub sites of the airways but without associated eosinophilia. There were no significant correlations between the fungal culture and clinical parameters of CRS nor were there significant correlations between fungal culture and objective lower airway involvement.

Detection of Helicobacter pylori in the middle ear fluid of patients with otitis media with effusion.

OBJECTIVES: In patients with otitis media with effusion (OME), colonization of the middle ear effusion (MEE) by Helicobacter pylori (HP) was investigated. STUDY DESIGN: A prospective nonrandomized study with nonpaired, nonmatched controls. Smear preparations were immunostained with anti-HP antibody and were subjected to Gram staining and Giemsa staining. The rapid urease test (CLO) was done. RESULTS: Twelve of 15 smears for MEE were positive for HP by immunohistochemistry and 14 by Giemsa that were Gram-negative. In 3 with positive immunohistochemistry, the CLO was positive. CONCLUSION: The results suggest that HP may exist in the MEE of some patients with OME.

Microbial exposure, symptoms and inflammatory mediators in nasal lavage fluid of kitchen and clerical personnel in schools.

OBJECTIVES: The aim of this study was to investigate how the microbial conditions of kitchen facilities differ from those in other school facilities. The health status of the personnel was also studied. MATERIALS AND METHODS: The microbial investigations were conducted in six moisture-damaged schools and two reference schools. The symptoms of the kitchen personnel were surveyed with questionnaires and inflammatory responses in nasal lavage (NAL) fluid were measured. RESULTS: The total concentrations of airborne microbes were lower in kitchens than in other facilities of the schools. However, the occurrence of moisture damage increased the airborne microbial concentrations both in kitchens, and in other facilities. Bacterial concentrations were high on surfaces in the damaged kitchens. Gram-negative bacteria predominated, but also thermophilic bacteria and mycobacteria were detected. Respiratory and general symptoms were prevalent both among kitchen workers and clerical personnel in the moisture-damaged environments. Reported allergies and repeated respiratory infections were connected with high IL-4 concentrations in NAL fluid. Median concentrations of studied inflammatory mediators (NO, IL-4, IL-6 and TNF-alpha) were slightly higher in NAL samples of kitchen workers than among the clerical personnel. CONCLUSIONS: Kitchen facilites differ from other facilities of the school building for their moisture conditions and microbial contamination. Thus, they represent a specific type of environment that may affect the health status of the personnel.

Relationships among bacteria, upper airway, lower airway, and systemic inflammation in COPD.

STUDY OBJECTIVE: The upper and lower airways are continuous. While upper airway symptoms are common in COPD patients, with accumulating evidence to suggest increased nasal inflammation, the relationships among upper airway, lower airway, and systemic inflammatory indexes have not been studied. We aimed to confirm that there is heightened nasal inflammation in COPD patients, to test the hypothesis that the degree of upper airway inflammation relates to the degree of lower airway inflammation, and to investigate the underlying associations with bacterial carriage and the systemic inflammatory response. DESIGN: Prospective cohort study. SETTING: Outpatient Department, London Chest Hospital, London, UK. PARTICIPANTS: Forty-seven patients with COPD and 12 control subjects of similar age, sex, and smoking status. MEASUREMENTS: Serum, nasal wash fluid, and sputum samples were obtained from 47 stable patients with COPD for the analysis of inflammatory indexes and bacterial colonization. Nasal wash fluid specimens were obtained from 12 control subjects. RESULTS: COPD patients had an increased nasal interleukin (IL)-8 concentration compared to control subjects (difference, 97.2 pg/mL; p = 0.009). The nasal IL-8 concentration in COPD patients correlated with that in sputum (r = 0.30; p = 0.039). In both the upper and lower airways of patients with COPD, the IL-8 concentration was associated with indexes of bacterial colonization. Patients colonized with a sputum potentially pathogenic microorganism had a higher total nasal bacterial load (difference, 1.5 log cfu/mL; p = 0.016). We did not find significant relationships between the degree of upper or lower airway inflammation, or bacterial carriage, and the systemic inflammatory response. CONCLUSIONS: COPD is associated with an increased nasal concentration of the neutrophil chemoattractant protein IL-8, the degree of which reflects that present in the lower airway. A relationship between lower airway bacterial colonization, postnasal drip, and higher nasal bacterial load may suggest a mechanism underlying this finding. This study is the first to report a correlation between the degree of upper and lower airway inflammation in COPD.

Th-1 and Th-2 cytokine production in infants with virus-associated wheezing.

Wheezing associated with respiratory viral infections in infancy is very common and results in high morbidity worldwide. The Th1/Th2 pattern of immune response in these patients remains unclear and previous studies have shown controversial results. The aim of the present study was to compare the type of Th1/Th2 cytokine response between infants with acute bronchiolitis, recurrent wheezing and upper respiratory infections from a developing country. Infants younger than 2 years of age admitted to Hospital São Lucas, Porto Alegre, RS, Brazil, between May and November 2001, with an acute episode of wheezing associated with viral respiratory infection were selected. Subjects with upper respiratory infections from the emergency department were selected for the control group. Interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) levels from nasal aspirates were determined by ELISA from peripheral mononuclear cell cultures. Twenty-nine subjects with acute bronchiolitis, 18 with recurrent wheezing and 15 with upper respiratory infections were enrolled. There were no differences in family history of atopy or parental smoking between groups. Oxygen requirement was similar for the acute bronchiolitis and recurrent wheezing groups. The percentage of positive tests for the cytokines studied and the IFN-gamma/IL-4 ratio was similar for all groups. Comparison of the polarized Th1/Th2 cytokine results for the various groups showed no specific pattern of cytokine production. Infants with wheezing from a developing country do not show any specific predominant pattern of Th1/Th2 cytokine production, suggesting that multiple factors may be involved in the pathogenesis of this illness.

Th-1 and Th-2 cytokine production in infants with virus-associated wheezing

Wheezing associated with respiratory viral infections in infancy is very common and results in high morbidity worldwide. The Th1/Th2 pattern of immune response in these patients remains unclear and previous studies have shown controversial results. The aim of the present study was to compare the type of Th1/Th2 cytokine response between infants with acute bronchiolitis, recurrent wheezing and upper respiratory infections from a developing country. Infants younger than 2 years of age admitted to Hospital São Lucas, Porto Alegre, RS, Brazil, between May and November 2001, with an acute episode of wheezing associated with viral respiratory infection were selected. Subjects with upper respiratory infections from the emergency department were selected for the control group. Interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) levels from nasal aspirates were determined by ELISA from peripheral mononuclear cell cultures. Twenty-nine subjects with acute bronchiolitis, 18 with recurrent wheezing and 15 with upper respiratory infections were enrolled. There were no differences in family history of atopy or parental smoking between groups. Oxygen requirement was similar for the acute bronchiolitis and recurrent wheezing groups. The percentage of positive tests for the cytokines studied and the IFN-gamma/IL-4 ratio was similar for all groups. Comparison of the polarized Th1/Th2 cytokine results for the various groups showed no specific pattern of cytokine production. Infants with wheezing from a developing country do not show any specific predominant pattern of Th1/Th2 cytokine production, suggesting that multiple factors may be involved in the pathogenesis of this illness.