Cell Therapy with Bone Marrow Mononuclear Cells in Elastase-Induced Pulmonary Emphysema

Emphysema is characterized by destruction of alveolar walls with loss of gas exchange surface and consequent progressive dyspnea. This study aimed to evaluate the efficiency of cell therapy with bone marrow mononuclear cells (BMMC) in an animal model of elastase-induced pulmonary emphysema. Emphysema was induced in C57Bl/J6 female mice by intranasal instillation of elastase. After 21 days, the mice received bone marrow mononuclear cells from EGFP male mice with C57Bl/J6 background. The groups were assessed by comparison and statistically significant differences (p & 0. 05) were observed among the groups treated with BMMC and evaluated after 7, 14 and 21 days. Analysis of the mean linear intercept (Lm) values for the different groups allowed to observe that the group treated with BMMC and evaluated after 21 days showed the most significant result. The group that received no treatment showed a statistically significant difference when compared to other groups, except the group treated and evaluated after 21 days, evidencing the efficacy of cell therapy with BMMC in pulmonary emphysema. © 2012 Springer Science+Business Media New York.

Case report: Disseminated Mycobacterium tuberculosis infection in a dog

An uncommon disseminated Mycobacterium tuberculosis infection is described in a 12-year-old female dog presenting with fever, dyspnea, cough, weight loss, lymphadenopathy, melena, epistaxis, and emesis. The dog had a history of close contact with its owner, who died of pulmonary tuberculosis. Radiographic examination revealed diffuse radio-opaque images in both lung lobes, diffuse visible masses in abdominal organs, and hilar and mesenteric lymphadenopathy. Bronchial washing samples and feces were negative for acid-fast organisms. Polymerase chain reaction (PCR)-based species identification of bronchial washing samples, feces, and urine revealed M. tuberculosis using PCR-restriction enzyme pattern analysis-PRA. Because of public health concerns, which were worsened by the physical condition of the dog, euthanasia of the animal was recommended. Rough and tough colonies suggestive of M. tuberculosis were observed after microbiological culture of lung, liver, spleen, heart, and lymph node fragments in Löwenstein-Jensen and Stonebrink media. The PRA analysis enabled diagnosis of M. tuberculosis strains isolated from organs. Copyright © 2013 by The American Society of Tropical Medicine and Hygiene.

The role of leukotriene B4 in early stages of experimental paracoccidioidomycosis induced in phenotypically selected mouse strains

Paracoccidioidomycosis is a human systemic mycosis caused by the fungus Paracoccidioides brasiliensis. The mechanisms involved in innate immune response to this fungus are not fully elucidated. Leukotrienes are known to be critical for the clearance of various microorganisms, mainly by mediating the microbicidal function of phagocytes. We investigated the involvement of leukotriene B4 in the early stages of experimental paracoccidioidomycosis, which was induced by intratracheal inoculation of the fungus in selected mouse lines. The mouse lines utilized were produced through bi-directional phenotypic selection, endowed with maximal or minimal acute inflammatory reactivity, and designated AIRmax and AIRmin, respectively. AIRmax mice were more resistant to the infection, which was demonstrated by reduced lung fungal loads. However, the two lines produced similar amounts of leukotriene B4, and pharmacological inhibition of this mediator provoked similar fungal load increases in the two lines. The lower fungal load in the AIRmax mice was associated with a more effective inflammatory response, which was characterized by enhanced recruitment and activation of phagocytic cells and an increased production of activator cytokines. This process resulted in an increased release of fungicidal molecules and a diminution of fungal load. In both lines, leukotriene production was associated with a protective response in the lung that was consequent to the effect of this eicosanoid on the influx and activation of phagocytes. © 2013 ISHAM.

Improvement in ARDS experimental model installation: Low mortality rate and maintenance of hemodynamic stability

Introduction: Many experimental models using lung lavage have been developed for the study of acute respiratory distress syndrome (ARDS). The original technique has been modified by many authors, resulting in difficulties with reproducibility. There is insufficient detail on the lung injury models used, including hemodynamic stability during animal preparation and drawbacks encountered such as mortality. The authors studied the effects of the pulmonary recruitment and the use of fixed tidal volume (Vt) or fixed inspiratory pressure in the experimental ARDS model installation. Methods: Adult rabbits were submitted to repeated lung lavages with 30 ml/kg warm saline until the ARDS definition (PaO2/FiO(2) <= 100) was reached. The animals were divided into three groups, according to the technique used for mechanical ventilation: 1) fixed Vt of 10 ml/kg; 2) fixed inspiratory pressure (IP) with a tidal volume of 10 ml/kg prior to the first lung lavage; and 3) fixed Vt of 10 ml/kg with pulmonary recruitment before the first lavage. Results: The use of alveolar recruitment maneuvers, and the use of a fixed Vt or IP between the lung lavages did not change the number of lung lavages necessary to obtain the experimental model of ARDS or the hemodynamic stability of the animals during the procedure. A trend was observed toward an increased mortality rate with the recruitment maneuver and with the use of a fixed IP. Discussion: There were no differences between the three study groups, with no disadvantage in method of lung recruitment, either fixed tidal volume or fixed inspiratory pressure, regarding the number of lung lavages necessary to obtain the ARDS animal model. Furthermore, the three different procedures resulted in good hemodynamic stability of the animals, and low mortality rate. (C) 2012 Elsevier Inc. All rights reserved.

Alternative protocol to initiate high-frequency oscillatory ventilation: an experimental study

INTRODUCTION: The objective was to study the effects of a novel lung volume optimization procedure (LVOP) using high-frequency oscillatory ventilation (HFOV) upon gas exchange, the transpulmonary pressure (TPP), and hemodynamics in a porcine model of surfactant depletion. METHODS: With institutional review board approval, the hemodynamics, blood gas analysis, TPP, and pulmonary shunt fraction were obtained in six anesthetized pigs before and after saline lung lavage. Measurements were acquired during pressure-controlled ventilation (PCV) prior to and after lung damage, and during a LVOP with HFOV. The LVOP comprised a recruitment maneuver with a continuous distending pressure (CDP) of 45 mbar for 2.5 minutes, and a stepwise decrease of the CDP (5 mbar every 5 minute) from 45 to 20 mbar. The TPP level was identified during the decrease in CDP, which assured a change of the PaO2/FIO2 ratio < 25% compared with maximum lung recruitment at CDP of 45 mbar (CDP45). Data are presented as the median (25th-75th percentile); differences between measurements are determined by Friedman repeated-measures analysis on ranks and multiple comparisons (Tukey's test). The level of significance was set at P < 0.05. RESULTS: The PaO2/FiO2 ratio increased from 99.1 (56.2-128) Torr at PCV post-lavage to 621 (619.4-660.3) Torr at CDP45 (CDP45) (P < 0.031). The pulmonary shunt fraction decreased from 51.8% (49-55%) at PCV post-lavage to 1.03% (0.4-3%) at CDP45 (P < 0.05). The cardiac output and stroke volume decreased at CDP45 (P < 0.05) compared with PCV, whereas the heart rate, mean arterial pressure, and intrathoracic blood volume remained unchanged. A TPP of 25.5 (17-32) mbar was required to preserve a difference in PaO2/FIO2 ratio < 25% related to CDP45; this TPP was achieved at a CDP of 35 (25-40) mbar. CONCLUSION: This HFOV protocol is easy to perform, and allows a fast determination of an adequate TPP level that preserves oxygenation. Systemic hemodynamics, as a measure of safety, showed no relevant deterioration throughout the procedure.

Utility of a panviral microarray for detection of swine respiratory viruses in clinical samples

Several factors have recently converged, elevating the need for highly parallel diagnostic platforms that have the ability to detect many known, novel, and emerging pathogenic agents simultaneously. Panviral DNA microarrays represent the most robust approach for massively parallel viral surveillance and detection. The Virochip is a panviral DNA microarray that is capable of detecting all known viruses, as well as novel viruses related to known viral families, in a single assay and has been used to successfully identify known and novel viral agents in clinical human specimens. However, the usefulness and the sensitivity of the Virochip platform have not been tested on a set of clinical veterinary specimens with the high degree of genetic variance that is frequently observed with swine virus field isolates. In this report, we investigate the utility and sensitivity of the Virochip to positively detect swine viruses in both cell culture-derived samples and clinical swine samples. The Virochip successfully detected porcine reproductive and respiratory syndrome virus (PRRSV) in serum containing 6.10 × 10(2) viral copies per microliter and influenza A virus in lung lavage fluid containing 2.08 × 10(6) viral copies per microliter. The Virochip also successfully detected porcine circovirus type 2 (PCV2) in serum containing 2.50 × 10(8) viral copies per microliter and porcine respiratory coronavirus (PRCV) in turbinate tissue homogenate. Collectively, the data in this report demonstrate that the Virochip can successfully detect pathogenic viruses frequently found in swine in a variety of solid and liquid specimens, such as turbinate tissue homogenate and lung lavage fluid, as well as antemortem samples, such as serum.

Infections in lung and heart transplant recipients : Studies on the impact of bronchoscopy in the diagnosis of respiratory infections and detection of viral infections in blood and bronchoalveolar lavage fluid

Infection is a major cause of mortality and morbidity after thoracic organ transplantation. The aim of the present study was to evaluate the infectious complications after lung and heart transplantation, with a special emphasis on the usefulness of bronchoscopy and the demonstration of cytomegalovirus (CMV), human herpes virus (HHV)-6, and HHV-7. We reviewed all the consecutive bronchoscopies performed on heart transplant recipients (HTRs) from May 1988 to December 2001 (n = 44) and lung transplant recipients (LTRs) from February 1994 to November 2002 (n = 472). To compare different assays in the detection of CMV, a total of 21 thoracic organ transplant recipients were prospectively monitored by CMV pp65-antigenemia, DNAemia (PCR), and mRNAemia (NASBA) tests. The antigenemia test was the reference assay for therapeutic intervention. In addition to CMV antigenemia, 22 LTRs were monitored for HHV-6 and HHV-7 antigenemia. The diagnostic yield of the clinically indicated bronchoscopies was 41 % in the HTRs and 61 % in the LTRs. The utility of the bronchoscopy was highest from one to six months after transplantation. In contrast, the findings from the surveillance bronchoscopies performed on LTRs led to a change in the previous treatment in only 6 % of the cases. Pneumocystis carinii and CMV were the most commonly detected pathogens. Furthermore, 15 (65 %) of the P. carinii infections in the LTRs were detected during chemoprophylaxis. None of the complications of the bronchoscopies were fatal. Antigenemia, DNAemia, and mRNAemia were present in 98 %, 72 %, and 43 % of the CMV infections, respectively. The optimal DNAemia cut-off levels (sensitivity/specificity) were 400 (75.9/92.7 %), 850 (91.3/91.3 %), and 1250 (100/91.5 %) copies/ml for the antigenemia of 2, 5, and 10 pp65-positive leukocytes/50 000 leukocytes, respectively. The sensitivities of the NASBA were 25.9, 43.5, and 56.3 % in detecting the same cut-off levels. CMV DNAemia was detected in 93 % and mRNAemia in 61 % of the CMV antigenemias requiring antiviral therapy. HHV-6, HHV-7, and CMV antigenemia was detected in 20 (91 %), 11 (50 %), and 12 (55 %) of the 22 LTRs (median 16, 31, and 165 days), respectively. HHV-6 appeared in 15 (79 %), HHV-7 in seven (37 %), and CMV in one (7 %) of these patients during ganciclovir or valganciclovir prophylaxis. One case of pneumonitis and another of encephalitis were associated with HHV-6. In conclusion, bronchoscopy is a safe and useful diagnostic tool in LTRs and HTRs with a suspected respiratory infection, but the role of surveillance bronchoscopy in LTRs remains controversial. The PCR assay acts comparably with the antigenemia test in guiding the pre-emptive therapy against CMV when threshold levels of over 5 pp65-antigen positive leukocytes are used. In contrast, the low sensitivity of NASBA limits its usefulness. HHV-6 and HHV-7 activation is common after lung transplantation despite ganciclovir or valganciclovir prophylaxis, but clinical manifestations are infrequently linked to them.

Lung alveolar proteomics of bronchoalveolar lavage from a pulmonary alveolar proteinosis patient using high-resolution FTICR mass spectrometry

High-resolution Fourier transform ion cyclotron resonance (FTICR) mass spectrometry was developed and applied to the proteome analysis of bronchoalveolar lavage fluid (BALF) from a patient with pulmonary alveolar proteinosis. With use of 1-D and 2-D gel electrophoresis, surfactant protein A (SP-A) and other surfactant-related lung alveolar proteins were efficiently separated and identified by matrix-assisted laser desorption/ionization FTICR mass spectrometry . Low molecular mass BALF proteins were separated using a gradient 2-D gel. An efficient extraction/precipitation system was developed and used for the enrichment of surfactant proteins. The result of the BALF proteome analysis show the presence of several isoforms of SP-A, in which an N-non-glycosylierte form and several proline hydroxylations were identified. Furthermore, a number of protein spots were found to contain a mixture of proteins unresolved by 2-D gel electrophoresis, illustrating the feasibility of high-resolution mass spectrometry to provide identifications of proteins that remain unseparated in 2-D gels even upon extended pH gradients.

Oxidative stress in lavage fluid of preterm infants at risk of chronic lung disease

There is evidence that oxidative stress plays a role in the development of chronic lung disease (CLD), with immature lungs being particularly sensitive to the injurious effect of oxygen and mechanical ventilation. We analyzed total ascorbate, urate, and protein carbonyls in 102 bronchoalveolar lavage fluid samples from 38 babies (33 preterm, 24–36 wk gestation; 5 term, 37–39 wk gestation). Preterm babies had significantly decreasing concentrations of ascorbate, urate, and protein carbonyls during the first 9 days of life (days 1–3, 4–6, and 7–9, Kruskal-Wallis ANOVA: P 5 0.016, P , 0.0001, and P 5 0.010, respectively). Preterm babies had significantly higher protein carbonyl concentrations at days 1–3 and 4–6 (P 5 0.005 and P 5 0.044) compared with term babies. Very preterm babies (24–28 wk gestation) had increased concentrations of protein carbonyls at days 4–6 (P 5 0.056) and significantly decreased ascorbate concentrations at days 4–6 (P 5 0.004) compared with preterm babies (29–36 wk gestation). Urate concentrations were significantly elevated at days 1–3 (P 5 0.023) in preterm babies who subsequently developed CLD. This study has shown the presence of oxidative stress in the lungs of preterm babies during ventilation, especially in those who subsequently developed CLD.

Effect of bronchoalveolar lavage-directed therapy on pseudomonas aeruginosa infection and structural lung injury in children with cystic fibrosis

Context Early pulmonary infection in children with cystic fibrosis leads to increased morbidity and mortality. Despite wide use of oropharyngeal cultures to identify pulmonary infection, concerns remain over their diagnostic accuracy. While bronchoalveolar lavage (BAL) is an alternative diagnostic tool, evidence for its clinical benefit is lacking.

Objective To determine if BAL-directed therapy for pulmonary exacerbations during the first 5 years of life provides better outcomes than current standard practice relying on clinical features and oropharyngeal cultures.

Design, Setting, and Participants The Australasian Cystic Fibrosis Bronchoalveolar Lavage (ACFBAL) randomized controlled trial, recruiting infants diagnosed with cystic fibrosis through newborn screening programs in 8 Australasian cystic fibrosis centers. Recruitment occurred between June 1, 1999, and April 30, 2005, with the study ending on December 31, 2009.

Interventions BAL-directed (n=84) or standard (n=86) therapy until age 5 years. The BAL-directed therapy group underwent BAL before age 6 months when well, when hospitalized for pulmonary exacerbations, if Pseudomonas aeruginosa was detected in oropharyngeal specimens, and after P aeruginosa eradication therapy. Treatment was prescribed according to BAL or oropharyngeal culture results.

Main Outcome Measures Primary outcomes at age 5 years were prevalence of P aeruginosa on BAL cultures and total cystic fibrosis computed tomography (CF-CT) score (as a percentage of the maximum score) on high-resolution chest CT scan.

Results Of 267 infants diagnosed with cystic fibrosis following newborn screening, 170 were enrolled and randomized, and 157 completed the study. At age 5 years, 8 of 79 children (10%) in the BAL-directed therapy group and 9 of 76 (12%) in the standard therapy group had P aeruginosa in final BAL cultures (risk difference, −1.7% [95% confidence interval, −11.6% to 8.1%]; P=.73). Mean total CF-CT scores for the BAL-directed therapy and standard therapy groups were 3.0% and 2.8%, respectively (mean difference, 0.19% [95% confidence interval, −0.94% to 1.33%]; P=.74).

Conclusion Among infants diagnosed with cystic fibrosis, BAL-directed therapy did not result in a lower prevalence of P aeruginosa infection or lower total CF-CT score when compared with standard therapy at age 5 years.

Trial Registration anzctr.org.au Identifier: ACTRN12605000665639

Maintenance of end-expiratory recruitment with increased respiratory rate after saline-lavage lung injury

Cyclical recruitment of atelectasis with each breath is thought to contribute to ventilator-associated lung injury. Extrinsic positive end-expiratory pressure (PEEPe) can maintain alveolar recruitment at end exhalation, but PEEPe depresses cardiac output and increases overdistension. Short exhalation times can also maintain end-expiratory recruitment, but if the mechanism of this recruitment is generation of intrinsic PEEP (PEEPi), there would be little advantage compared with PEEPe. In seven New Zealand White rabbits, we compared recruitment from increased respiratory rate (RR) to recruitment from increased PEEPe after saline lavage. Rabbits were ventilated in pressure control mode with a fraction of inspired O(2) (Fi(O(2))) of 1.0, inspiratory-to-expiratory ratio of 2:1, and plateau pressure of 28 cmH(2)O, and either 1) high RR (24) and low PEEPe (3.5) or 2) low RR (7) and high PEEPe (14). We assessed cyclical lung recruitment with a fast arterial Po(2) probe, and we assessed average recruitment with blood gas data. We measured PEEPi, cardiac output, and mixed venous saturation at each ventilator setting. Recruitment achieved by increased RR and short exhalation time was nearly equivalent to recruitment achieved by increased PEEPe. The short exhalation time at increased RR, however, did not generate PEEPi. Cardiac output was increased on average 13% in the high RR group compared with the high PEEPe group (P < 0.001), and mixed venous saturation was consistently greater in the high RR group (P < 0.001). Prevention of end-expiratory derecruitment without increased end-expiratory pressure suggests that another mechanism, distinct from intrinsic PEEP, plays a role in the dynamic behavior of atelectasis.

Alterations of alveolar type II cells and intraalveolar surfactant after bronchoalveolar lavage and perfluorocarbon ventilation. An electron microscopical and stereological study in the rat lung

BACKGROUND: Repeated bronchoalveolar lavage (BAL) has been used in animals to induce surfactant depletion and to study therapeutical interventions of subsequent respiratory insufficiency. Intratracheal administration of surface active agents such as perfluorocarbons (PFC) can prevent the alveolar collapse in surfactant depleted lungs. However, it is not known how BAL or subsequent PFC administration affect the intracellular and intraalveolar surfactant pool. METHODS: Male wistar rats were surfactant depleted by BAL and treated for 1 hour by conventional mechanical ventilation (Lavaged-Gas, n = 5) or partial liquid ventilation with PF 5080 (Lavaged-PF5080, n = 5). For control, 10 healthy animals with gas (Healthy-Gas, n = 5) or PF5080 filled lungs (Healthy-PF5080, n = 5) were studied. A design-based stereological approach was used for quantification of lung parenchyma and the intracellular and intraalveolar surfactant pool at the light and electron microscopic level. RESULTS: Compared to Healthy-lungs, Lavaged-animals had more type II cells with lamellar bodies in the process of secretion and freshly secreted lamellar body-like surfactant forms in the alveoli. The fraction of alveolar epithelial surface area covered with surfactant and total intraalveolar surfactant content were significantly smaller in Lavaged-animals. Compared with Gas-filled lungs, both PF5080-groups had a significantly higher total lung volume, but no other differences. CONCLUSION: After BAL-induced alveolar surfactant depletion the amount of intracellularly stored surfactant is about half as high as in healthy animals. In lavaged animals short time liquid ventilation with PF5080 did not alter intra- or extracellular surfactant content or subtype composition.

BRONCHOALVEOLAR LAVAGE AND GALLIUM-67 LUNG SCANNING IN THE EVALUATION OF ASBESTOS-EXPOSED INDIVIDUALS

In this study, an attempt is made to evaluate certain parameters that might indicate the beginning of a certain fibrogenic activity in the lung parenchyma, even before such changes become visible on the chest x-ray. The hypothesis is that studies such as certain bronchoalveolar immunological characteristics and Gallium-67 lung scans may be more sensitive indicators of parenchymal lung damage in response to asbestos inhalation than conventional radiographic criteria. If so, then in those cases where the criteria for the diagnosis of asbestosis lack the presence of parenchymal changes, it would be unwise to deny the diagnosis unless further investigations, such as the bronchoalveolar lavage fluid analysis and the Gallium-67 lung scan techniques, are made available.^ Four groups of individuals have been included in this study. The volunteer group showing no history of asbestos exposure with normal chest x-rays has been used as a normal healthy comparison group. The other three groups are all asbestos-exposed but differ as to their findings in the chest radiographs. One has parenchymal changes (0/1 or more, ILO Classification), the second has no parenchymal but pleural changes, and the third has neither.^ The most significant laboratory parameter for bronchoalveolar lavage, in this study, is that of Neutrophils (PMNs). All three asbestos-exposed groups showed no differences when compared with each other, while such differences were statistically significant when such groups were separately compared with the normal comparison group. A similar finding existed also when the Helper: Suppressor T-Cell ratios were compared, and found to be higher in all the asbestos-exposed groups.^ Another sensitive test is that of Gallium-67 lung scan. This was found to be positive in some patients where parenchymal changes were absent. Even in some of those who showed neither parenchymal nor pleural changes in their chest x-ray showed positive test results. Such changes indicate a state of an underlying pathogenic process that is still undetectable by conventional radiography. This highly recommends the future application of such tests for the early detection of active pulmonary disease, especially in those who show no parenchymal changes in their chest x-rays. (Abstract shortened with permission of author.) ^

The effect of endotracheal suction on regional tidal ventilation and end-expiratory lung volume

Purpose: To examine the impact of different endotracheal tube (ETT) suction techniques on regional end-expiratory lung volume (EELV) and tidal volume (VT) in an animal model of surfactant-deficient lung injury. Methods: Six 2-week old piglets were intubated (4.0 mm ETT), muscle-relaxed and ventilated, and lung injury was induced with repeated saline lavage. In each animal, open suction (OS) and two methods of closed suction (CS) were performed in random order using both 5 and 8 French gauge (FG) catheters. The pre-suction volume state of the lung was standardised on the inflation limb of the pressure-volume relationship. Regional EELV and VT expressed as a proportion of the impedance change at vital capacity (%ZVCroi) within the anterior and posterior halves of the chest were measured during and for 60 s after suction using electrical impedance tomography. Results: During suction, 5 FG CS resulted in preservation of EELV in the anterior (nondependent) and posterior(dependent) lung compared to the other permutations, but these only reached significance in the anterior regions (p\0.001 repeated-measures ANOVA). VT within the anterior, but not posterior lung was significantly greater during 5FG CS compared to 8 FG CS; the mean difference was 15.1 [95% CI 5.1, 25.1]%ZVCroi. Neither catheter size nor suction technique influenced post-suction regional EELV or VT compared to pre-suction values (repeated-measures ANOVA). Conclusions: ETT suction causes transient loss of EELV and VT throughout the lung. Catheter size exerts a greater influence than suction method, with CS only protecting against derecruitment when a small catheter is used, especially in the non-dependent lung.

Adenovirus species C is associated with chronic suppurative lung diseases in children

Background The role of human adenoviruses (HAdVs) in chronic respiratory disease pathogenesis is recognized. However, no studies have performed molecular sequencing of HAdVs from the lower airways of children with chronic endobronchial suppuration. We thus examined the major HAdV genotypes/species, and relationships to bacterial coinfection, in children with protracted bacterial bronchitis (PBB) and mild bronchiectasis (BE). Methods Bronchoalveolar lavage (BAL) samples of 245 children with PBB or mild (cylindrical) BE were included in this prospective cohort study. HAdVs were genotyped (when possible) in those whose BAL had HAdV detected (HAdV+). Presence of bacterial infection (defined as ≥104 colony-forming units/mL) was compared between BAL HAdV+ and HAdV negative (HAdV−) groups. Immune function tests were performed including blood lymphocyte subsets in a random subgroup. Results Species C HAdVs were identified in 23 of 24 (96%) HAdV+ children; 13 (57%) were HAdV-1 and 10 (43%) were HAdV-2. An HAdV+ BAL was significantly associated with bacterial coinfection with Haemophilus influenzae, Moraxella catarrhalis, or Streptococcus pneumoniae (odds ratio [OR], 3.27; 95% confidence interval, 1.38–7.75; P = .007) and negatively associated with Staphylococcus aureus infection (P = .03). Young age was related to increased rates of HAdV+. Blood CD16 and CD56 natural killer cells were significantly more likely to be elevated in those with HAdV (80%) compared with those without (56.1%) (P = .027). Conclusions HAdV-C is the major HAdV species detected in the lower airways of children with PBB and BE. Younger age appears to be an important risk factor for HAdV+ of the lower airways and influences the likelihood of bacterial coinfection