Major Airway Research Articles

Second-Generation Supraglottic Airway Devices Versus Endotracheal Intubation in Adults Undergoing Abdominopelvic Surgery: A Systematic Review and Meta-Analysis

BACKGROUND: Second-generation supraglottic airway (SGA) devices are widely used, but thought to have inferior safety performance to endotracheal tubes (ETTs), but might be equally efficacious while improving patient-centered outcomes. We compared second-generation SGAs with ETTs for perioperative safety, efficacy, and quality of recovery in adults undergoing abdominopelvic surgery under general anesthesia. Our primary objective was to assess safety in the form of major airway complications. Secondary objectives were other safety, efficacy, and quality of recovery outcomes. METHODS: We searched 4 databases for randomized controlled trials of adult patients having abdominopelvic surgery comparing second-generation SGAs and ETTs. After 2-person screening and data extraction, pairwise meta-analysis was conducted and the grading of recommendations, assessment, development, and evaluation (GRADE) approach was applied to assess the certainty of evidence. RESULTS: A total of 51 studies, randomizing 5110 patients, were included. Second-generation SGAs significantly reduced the risk of major perioperative airway complications (risk ratio [RR], 0.41; 95% confidence interval [CI], 0.23–0.71; P = .007; low certainty), with no clear clinically relevant difference in regurgitation or pulmonary aspiration (low certainty). SGAs significantly increased the risk of inadequate ventilation (RR, 3.36; 95% CI, 1.43–7.89; P = .011; very low certainty); however, postoperative sore throat (RR, 0.52; 95% CI, 0.38–0.70; P < .001; moderate certainty), hoarseness (RR, 0.32; 95% CI, 0.231–0.48; P < .001; low certainty), coughing at the emergence of anesthesia (RR, 0.17; 95% CI, 0.08–0.36; P < .001; low certainty), and postoperative nausea and vomiting (RR, 0.64; 95% CI, 0.42–0.98; P = .042; very low certainty) were all less frequent with SGAs. No other clinically relevant differences were observed for other remaining outcomes. CONCLUSIONS: Second-generation SGAs reduce the risk of major airway complications compared with ETTs in adults undergoing abdominopelvic procedures under general anesthesia, with no reported clinically relevant differences in the risk of regurgitation or pulmonary aspiration. Additionally, they improve the quality of postoperative recovery with lower risk of sore throat, hoarseness, and postoperative nausea and vomiting. These data provide an opportunity for clinicians to reassess the implications of conservative airway management, and potentially expand the role of second-generation SGAs in routine clinical practice.

Major Airway Injury—Case Series and Review of Literature

Major Airway Injury—Case Series and Review of Literature

Comparison of Macintosh Laryngoscope, King Vision®, VividTrac®, AirAngel Blade®, and a Custom-Made 3D-Printed Video Laryngoscope for Difficult and Normal Airways in Mannequins by Novices-A Non-Inferiority Trial.

Background: Endotracheal intubation (ETI) is a cornerstone of airway management. The gold standard device for ETI is still the direct laryngoscope (DL). However, video laryngoscopes (VLs) are now also widely available and have several proven advantages. The VL technique has been included in the major airway management guidelines. During the COVID-19 pandemic, supply chain disruption has raised demand for 3D-printed medical equipment, including 3D-printed VLs. However, studies on performance are only sparsely available; thus, we aimed to compare 3D-printed VLs to the DL and other VLs made with conventional manufacturing technology. Methods: Forty-eight medical students were recruited to serve as novice users. Following brief, standardized training, students executed ETI with the DL, the King Vision® (KV), the VividTrac® (VT), the AirAngel Blade® (AAB), and a custom-made 3D-printed VL (3DVL) on the Laerdal® airway management trainer in normal and difficult airway scenarios. We evaluated the time to and proportion of successful intubation, the best view of the glottis, esophageal intubation, dental trauma, and user satisfaction. Results: The KV and VT are proved to be superior (p < 0.05) to the DL in both scenarios. The 3DVL's performance was similar (p > 0.05) or significantly better than that of the DL and mainly non-inferior (p > 0.05) compared to the KV and VT in both scenarios. Regardless of the scenario, the AAB proved to be inferior (p < 0.05) even to the DL in the majority of the variables. The differences between the devices were more pronounced in the difficult airway scenario. The user satisfaction scores were in concordance with the aforementioned performance of the scopes. Conclusions: Based upon our results, we cannot recommend the AAB over the DL, KV, or VT. However, as the 3DVL showed, 3D printing indeed can provide useful or even superior VLs, but prior to clinical use, meticulous evaluation might be recommended.

Scope of a short &amp; obese patient for thymoma surgery with the risk of difficulty in weaning from general anaesthesia

Obese patients had more difficulty with tracheal intubation and a higher incidence of post-extubation stridor. Obesity is such a ubiquitous issue in our culture, and it is a significant risk factor for many diseases, thus it is not surprising that many obese patients are treated in ICU. The objective of this article is to explore challenges for short, obese patients (Little’s) in the critical care setting. Obese patients have a strong correlation between lung function and body fat distribution, with greater impairment when fat accumulates in the chest and abdomen. Mediastinal masses, particularly those located in the anterior mediastinum, can cause perioperative morbidity and mortality by causing major airway and vascular compression, which may be exacerbated under general anesthesia.

The innominate artery, a seemingly benign artery that can cause major airway complications.

The innominate artery, a seemingly benign artery that can cause major airway complications.

Regional lung targeting with a fluticasone/salmeterol aerosol using a bolus breath hold method of the PreciseInhale® system: A first evaluation in humans

BackgroundIn development of inhaled drugs- and formulations the measured concentration in the systemic circulation is often used as a surrogate for local dosimetry in the lungs. To further elucidate regional differences in the fate of drugs in the lungs, different aerodynamic sizes of aerosols have been used to target major airway regions. An alternative approach to achieve regional targeting of aerosols, is to use a defined aerosol bolus together with a bolus breath hold strategy. A small volume of test aerosol is intercalated and stopped at different penetration depths, to achieve increased drug deposition at chosen lung locations. Drug permeation from the lung regions is then investigated by repeatedly sampling venous blood from the systemic circulation.The PreciseInhale® (PI) exposure platform was developed to allow generation of aerosols from different sources, including clinical inhalers, into a holding chamber, for subsequent use with alternative exposure modules in vitro and in vivo. In the current first-in-human study was investigated the feasibility of a new clinical exposure module added to the PI system. By extracting aerosol puffs from a medical inhaler for subsequent delivery to volunteers, it was possible to administer whole lung exposures, as well as regional targeting exposures. MethodsAerosols containing 250 µg/25 µg fluticasone propionate (FP)/salmeterol xinafoate (SMX) were automatically actuated and extracted from the pressurized Metered Dose Inhaler (pMDI) Evohaler Seretide forte into the PI system's holding chamber, then administered to the healthy volunteers using controlled flowrate and volume exposure cycles.Two main comparisons were made by measuring the systemic PK response: I. One label dose directly from the inhaler to the subject was compared to the same dose extracted from the pMDI into the PI system and then administered to the subject. II A small aerosol bolus at a penetration level in the central airways was compared to a small aerosol bolus at a penetration level in the peripheral lung. Results and ConclusionsWhen one inhaler dose was administered via the PI system, the absorbed dose, expressed as AUC24, was approximately twice as high and the CV was less than half, compared to direct inhalation from the same pMDI. Bolus breath hold targeting of drugs from the same aerosol mixture to the peripheral lung and the central airways showed a difference in their appearance in the systemic circulation. Normalized to the same deposited dose, SMX had a 57 % higher Cmax in the peripheral lung compared to the central airways. However, from 6 to 24 h after dosing the systemic concentrations of SMX from both regions were quite similar. FP had parallel concentrations curves with a 23 % higher AUC24 in the peripheral lung with no noticeable elevation around Cmax. The permeability of these two substances from similar sized aerosols was indeed higher in the thinner air/blood barriers of the peripheral lung compared to the central airways, but differences as measured on the venous side of the circulation were not dramatic. In conclusion, the PI system provided better control of actuation, aspiration, and dispensation of aerosols from the clinical inhaler and thereby delivered higher quality read outs of pharmacokinetic parameters such as tmax, Cmax, and AUC. Improved performance, using PI system, can likely also be employed for studying regional selectivity of other responses in the lungs, for use in drug development.

Mounier-Kuhn syndrome: A case report of a 64-year-old male followed up after 8 years of the first diagnosis

Mounier-Kuhn Syndrome (MKS) is a rare congenital disorder characterized by the abnormal dilatation of the major airways, namely trachea and stem bronchi. It can be presented as the recurrent lower respiratory tract infection. Symptoms may vary from being asymptomatic to a wide range of infections which may lead to severe respiratory failure. Diagnosis can be performed by the means of computed tomography and bronchoscopy. The treatment is primarily symptomatic and supportive. Herein, we have presented a case of a 64-years old man, ex-smoker, who was referred after 4 episodes of antibiotic treated pulmonary infection. He was previously diagnosed with tracheobronchomegaly through CT scan in 2015. We have compared the lung function test and the radiological features between two time slots being 8 years apart (2015-2023), that showed insignificant change.

An Unknown Foreign laryngeal Object: an exotic complication of skull base osteoradionecrosis

BackgroundOsteoradionecrosis (ORN) of the skull base is a rare complication after head and neck radiation with a broad variety of subsequent complications.MethodsA 68-year-old woman with a complex oncological history (right-sided sphenoid meningioma; left-sided neck metastasis of a Cancer of Unknown Primary—CUP) was admitted with a right-sided epi—/ oropharyngeal mass and severe pain exacerbations for further evaluation. CT scan revealed an advanced ORN of the skull base with subsequent abruption of the ventral part of the clivus. This dislocated part of the clivus wedged in the oropharynx for 48 h and then moved towards the larynx, resulting in dyspnea and almost complete airway obstruction.ResultsDue to the dangerous airway situation, an urgent exploration and removal of the dislocated clivus was necessary. After a potential cervical spine instability was ruled out, the patient’s airway was initially secured with an awake tracheotomy and the clivus was removed transorally. The tracheostomy tube was removed during the ongoing inpatient stay, and the patient was discharged with significant pain relief.ConclusionsThe present case illustrates an orphan complication of skull base ORN resulting in a major airway emergency situation.

Fine‐scale distribution of the lungworm Halocercus delphini in the lungs of the striped dolphin, Stenella coeruleoalba: implications about migration pathways and functional significance

AbstractDespite their high pathogenicity, limited knowledge is available on intrahost migration pathways and microhabitat distribution of pseudaliid lungworms. In this study, the distribution of Halocercus delphini in the lungs of the striped dolphin, Stenella coeruleoalba, was analyzed on three scales: between the right and left lungs, within the lungs, and between worm clusters. Evidence of a relationship between the distribution of H. delphini and the perfusion of the lungs of S. coeruleoalba is provided by the consistent correlation of these two factors, both on a longitudinal scale and by the difference in parasite burden between the left and right lung. This relationship, when coupled with the nested pattern of colonization, suggests that this species, like many other metastrongyloids, migrates to the lungs via the circulatory system. Additionally, the concentration of lungworms around the major airways could be a further reflection of the well‐perfused nature of these passageways. Equally, this distribution could be a strategy to minimize the distance that larvae must travel to exit the lungs via the trachea, as do most other metastrongyloids. On a more localized scale, the tendency of H. delphini to form distinct heterosexual clusters even at low infection intensities indicates active mate‐seeking behavior for reproduction.

Impacted Foreign body of Porcupine spine in Neck- a case report

Abstract: Introduction: Trauma and foreign body impaction in the neck can be dangerous because of high chances of injury to vital structures like the major blood vessels, airway, digestive tract and nerves located in the neck. Hence, early diagnosis and treatment is important to prevent severe morbidity and mortality. Case presentation: A 24 years old male from Rolpa had presented with complaint of painful swelling over right side of neck for a week.He had past history of encounter with porcupine a month back. Ultrasonography of the neck revealed impaction of foreign body in the right lateral neck(sternocleidomastoid muscle) with pus and granulation tissue around it. He was then admitted and exploration under general anesthesia was done and porcupine spine was removed. Conclusion: Any neck trauma should be evaluated for residual foreign body as it can be dangerous in the neck. Early detection and removal of foreign body should be done on time to prevent life threatening complications.

Open Surgical Retrieval of a Foreign Body in the Neck: A Case Report

Foreign body retention in the neck may be either traumatic or iatrogenic. Penetrating neck injuries with retained bodies are critical, as the neck serves as a passage for structures essential to life. Therefore, prompt detection and retrieval of the foreign body are paramount in preventing mortality. Here, authors present a case in which a successful surgical retrieval was performed without any postprocedural complications, despite the patient presenting relatively late after the injury. In this case report, a 23-year-old male labourer presented with a right-sided neck swelling two months after a workplace injury involving a shattered metal plate. Imaging confirmed a 15×5 mm hyperdense metallic object penetrating the sternocleidomastoid muscle. Successful open exploration extracted a 1.5 cm metallic shard at the C6 vertebral level, with no major vessel or airway damage. Postoperatively, the patient exhibited no movement restrictions, highlighting the atypical presentation of a retained metallic foreign body and the importance of timely intervention and comprehensive imaging for successful management.

Neurogenic tumours of the posterior mediastinum and differential diagnosis considerations.

The mediastinal compartment harbours vital organs and structures, including the heart, great vessels, major airways, and thymus. These structures are embedded in and associated with soft-tissue elements consisting of adipose and fibro-collagenous tissue in which soft-tissue tumours may develop. A detailed inventory of soft-tissue tumours that may be encountered in the mediastinum based on the WHO 2013 classification was published in 2015. In addition, several comprehensive reviews on mediastinal soft-tissue pathology are available, including reviews focusing specifically on a single tumour type. This review will focus on primary neurogenic and spindle cell tumours of the somatic soft tissue of the posterior mediastinum and provide a discussion of the pertinent differential diagnoses.

Lung Sparing Bronchoplasty of Carcinoid Tumors with Single Lumen ETT in a Limited-Resource Hospital Setting

Two patients, who presented with complaints of cough and hemoptysis, were diagnosed as having biopsy proven carcinoid tumor of the airway. Both patients underwent lung sparing surgery and bronchoplasty, with the aid of single lumen ETT in a limited resource, underprivileged hospital setting. This case report underscores the management of resectable tumors of major airways with single lumen ETT.

Plastic bronchitis during childhood: Diversity of presentation, etiology, treatment, and outcomes.

Plastic bronchitis (PB) is a rare disease in children, and reliable data are scarce. Here, we aimed to analyze the clinical features, management, and outcomes in children with PB. The medical data of patients who were followed up with a diagnosis of PB between January 2010 and March 2022 were retrospectively analyzed. The median age of 15 patients was 9 (interquartile range: 4-10) years with a male/female ratio of 12/3. Initial symptoms included recurrent pneumonia (33.3%), persistent atelectasis (33.3%), cast expectoration (26.6%), and intense, persistent cough (6.6%). The most common underlying diagnosis was asthma (n = 12, 80%), and six of the patients were newly diagnosed. The most common radiological findings were atelectasis as a consequence of major airway obstruction on chest X-ray or computed tomography. Five patients, all diagnosed as having asthma, had recurrent PB and required multiple airway procedures for treatment and diagnosis. During a median 7-year follow-up of five patients, occasionally cast expectoration was observed in one patient with asthma who had poor compliance with inhaled corticosteroids. PB is a common reflection of the different underlying etiologies in the pediatric age group, and treatment and outcomes are closely related to these. It should be kept in mind that asthma can be a predisposing factor for the development of PB.

Management of massive airway hemorrhage associated with extracorporeal membrane oxygenation: A retrospective case series study.

Extracorporeal membrane oxygenation (ECMO) is an important means of treating patients with respiratory failure. Massive airway hemorrhage is a rare complication of ECMO, with high mortality. The aim of this study was to provide a reference for improving the success rate of treatment of this complication by analyzing and summarizing patient clinical data. We searched PubMed, Medline, and EMBASE databases for case reports of massive airway bleeding associated with ECMO from January 2000 to January 2022 and included one case treated at our facility. All patients were disconnected from the ventilator, and the endotracheal tube was clamped during treatment, resulting in complete airway packing for hemostasis. The clinical data of these patients were analyzed. Through searching and further screening, two works of literature reported four cases that met our inclusion criteria. Including our patient's case, five patients were included in this study (four adults and one neonate). The longest ECMO treatment time before bleeding was 14 days, and the shortest was 20 min. In all patients, conservative treatment was ineffective after a major airway hemorrhage. They were disconnected from the ventilator and the tracheal tube was clamped for 13-72 h. The four adult patients underwent bronchial artery embolization in the interventional radiology suite. All patients' bleeding stopped after treatment; they were successfully weaned off ECMO and discharged. Treatment measures to disconnect the ventilator and clamp the endotracheal tube with full support from ECMO are feasible for massive airway bleeding associated with ECMO. Early bronchial arteriography and embolization can prevent rebleeding.

Altered differentiation in proximal airway epithelium in trisomy 21

Rationale: Trisomy 21 (T21), resulting in Down Syndrome (DS), is the most prevalent chromosomal abnormality worldwide. Recent studies have indicated that individuals with DS present with ciliopathies, as well as impaired mucociliary clearance. Whereas these defects have been determined in children, we recently reported that structural changes initiate prenatally in T21 lungs. Thus, our goal is to determine whether proximal airway differentiation and specifically ciliary structure and function are altered during T21 lung development. Methods: Immunofluorescent (IF) staining was performed on prenatal T21 and non-T21 age and sex matched control lungs to assess proximal airway cellular composition and differentiation. Gene expression was assessed by RT-qPCR. In vitro proximal airway differentiation was performed using primary basal cells isolated from prenatal T21 and non-T21 tracheas. Cells were plated into transwells and differentiated on air liquid interface (ALI). IF staining, RT-qPCR, and trans-epithelial electrical resistance (TEER) analyses were performed on ALI cultures at Day 0, 7, 14, and 21. Results: Prenatal T21 lungs were assessed for all major proximal airway cell types (basal, club, ciliated, goblet) and compared to non-T21 controls. IF staining of club cell markers (SCGB1A1, SCGB3A2) were increased in T21 lungs, with a significantly greater number of SCGB1A1 cells (p=0.0114) (n=20). A comparable trend was observed with goblet cells, which showed a larger quantifiable area of MUC5B staining in T21 lungs as compared to non-T21. These results were confirmed by RT-qPCR, which demonstrated a trend of increased expression for both SCGB3A2 and MUC5B, and a significant increase of SCGB1A1 (p=0.0169) (n=14). IF staining of ciliated cell markers (FOXJ1, RSPH1, ARL13B) were also increased in T21 lungs as compared to non-T21. These results were validated by RT-qPCR, with a significant increase in RSPH1, a gene responsible for motile cilia and encoded on chromosome 21 (p=0.0168) (n=11). We then cultured primary T21 and non-T21 basal cells in ALI and achieved successful airway epithelium differentiation. Confluent transwell IF staining shows a steady rate of P63+ cells, and an increase of ciliated cells (ARL13B, FOXJ1) over 21 days in culture. TEER measurements were lower in T21 cultures as compared to age matched non-T21. Conclusion: Our data demonstrate that prenatal T21 lungs undergo precocious proximal airway differentiation with possibly compromised tight junctions. These aberrancies may possibly contribute to the high infection rate, ciliopathies, and faulty mucociliary clearance observed in DS. California Institute for Regenerative Medicine (CIRM) EDUC4 - 12837 (CC) and NIH NHLBI/Office of the Director R01HL155104 (SD). This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Transcriptomic analysis identified SLC40A1 as a key iron metabolism-related gene in airway macrophages in childhood allergic asthma.

Introduction: Asthma is the most common chronic condition in children, with allergic asthma being the most common phenotype, accounting for approximately 80% of cases. Growing evidence suggests that disruption of iron homeostasis and iron regulatory molecules may be associated with childhood allergic asthma. However, the underlying molecular mechanism remains unclear. Methods: Three childhood asthma gene expression datasets were analyzed to detect aberrant expression profiles of iron metabolism-related genes in the airways of children with allergic asthma. Common iron metabolism-related differentially expressed genes (DEGs) across the three datasets were identified and were subjected to functional enrichment analysis. Possible correlations between key iron metabolism-related DEGs and type 2 airway inflammatory genes were investigated. Single-cell transcriptome analysis further identified major airway cell subpopulations driving key gene expression. Key iron metabolism-related gene SLC40A1 was validated in bronchoalveolar lavage (BAL) cells from childhood asthmatics with control individuals by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and immunofluorescence. The intracellular iron content in BAL cells was assessed by Perls iron staining and the iron levels in BAL supernatant was measured by iron assay to assess airway iron metabolism status in childhood asthmatics. Results: Five common iron metabolism-related DEGs were identified, which were functionally related to iron homeostasis. Among these genes, downregulated SLC40A1 was strongly correlated with type 2 airway inflammatory markers and the gene signature of SLC40A1 could potentially be used to determine type 2-high and type 2-low subsets in childhood allergic asthmatics. Further single-cell transcriptomic analysis identified airway macrophages driving SLC40A1 expression. Immunofluorescence staining revealed colocalization of FPN (encoded by SLC40A1) and macrophage marker CD68. Down-regulation of SLC40A1 (FPN) was validated by qRT-PCR and immunofluorescence analysis. Results further indicated reduced iron levels in the BAL fluid, but increased iron accumulation in BAL cells in childhood allergic asthma patients. Furthermore, decreased expression of SLC40A1 was closely correlated with reduced iron levels in the airways of children with allergic asthma. Discussion: Overall, these findings reveal the potential role of the iron metabolism-related gene SLC40A1 in the pathogenesis of childhood allergic asthma.

Tracheobronchial amyloidosis, isolated lung amyloidoma: invasive diagnostic and treatment

The article presents the latest trends of the diagnosis and treatment of tracheobronchial amyloidosis. Constriction of the bronchus due to amyloid deposits requires immunohistochemistry for protein typing. The only way of major airways recanalization is endoscopic surgical treatment. It is described the experience of treating four patients with tracheobronchial amyloidosis, in one of whom, a rare form of amyloidosis – lung amyloidoma developed.

Morphometry, gross morphology and available histopathology in North Atlantic right whale (Eubalaena glacialis) mortalities (1970-2002)

Fifty-four right whale mortalities have been reported from between Florida, USA and the Canadian Maritimes from 1970 to 2002. Thirty of those animals were examined: 18 adults and juveniles, and 12 calves. Morphometric data are presented such that prediction of body weight is possible if the age, or one or more measurements are known. Calves grew approximately linearly in their first year. Total length and fluke width increased asymptotically to a plateau with age, weight increased linearly with age, weight and snout to blowhole distance increased exponentially with total length, whereas total length was linearly related to fluke width and flipper length. Among the adults and juveniles examined in this study, human interaction appeared to be a major cause of mortality, where in 14/18 necropsies, trauma was a significant finding. In 10/14 of these, the cause of the trauma was presumed to be vessel collision. Entanglement in fishing gear accounted for the remaining four cases. Trauma was also present in 4/12 calves. In the majority of calf mortalities (8/12) the cause of death was not determined. Sharp ship trauma included propeller lacerations inducing multiple, deep lacerations that often incised vital organs including the brain, spinal cord, major airways, vessels and musculature. Blunt ship trauma resulted in major internal bruising and fractures often without any obvious external damage. In at least two cases fatal gear entanglements were extremely protracted: where the entanglements took at least 100 and 163 days respectively to be finally lethal. The sum of these findings show two major needs: (1) that extinction avoidance management strategies focused on reducing trauma to right whales from ship collisions and fishing gear entanglement are highly appropriate and need to be continued and; (2) that as mitigation measures continue to be introduced into shipping and fishing industry practices, there is a strong effort to maximise the diagnostic quality of post-mortem examination of right whale mortalities, to ensure an optimal understanding of resultant trends.

Real-time PCR has advantages over culture-based methods in identifying major airway bacterial pathogens in chronic obstructive pulmonary disease: Results from three clinical studies in Europe and North America.

We compared the performance of real-time PCR with culture-based methods for identifying bacteria in sputum samples from patients with chronic obstructive pulmonary disease (COPD) in three studies. This was an exploratory analysis of sputum samples collected during an observational study of 127 patients (AERIS; NCT01360398), phase 2 study of 145 patients (NTHI-004; NCT02075541), and phase 2b study of 606 patients (NTHI-MCAT-002; NCT03281876). Bacteria were identified by culture-based microbiological methods in local laboratories using fresh samples or by real-time PCR in a central laboratory using frozen samples. Haemophilus influenzae positivity with culture was differentiated from H. haemolyticus positivity by microarray analysis or PCR. The feasibility of bacterial detection by culture-based methods on previously frozen samples was also examined in the NTHI-004 study. Bacterial detection results from both culture-based and PCR assays were available from 2,293 samples from AERIS, 974 from the NTHI-004 study, and 1736 from the NTHI-MCAT-002 study. Quantitative real-time PCR (qPCR) showed higher positivity rates than culture for H. influenzae (percentages for each study: 43.4% versus 26.2%, 47.1% versus 23.6%, 32.7% versus 10.4%) and Moraxella catarrhalis (12.9% versus 6.3%, 19.0% versus 6.0%, 15.5% versus 4.1%). In the NTHI-004 and NTHI-MCAT-002 studies, positivity rates were higher with qPCR for Streptococcus pneumoniae (15.6% versus 6.1%, 15.5% versus 3.8%); in AERIS, a lower rate with qPCR than with culture (11.0% versus 17.4%) was explained by misidentification of S. pseudopneumoniae/mitis isolates via conventional microbiological methods. Concordance analysis showed lowest overall agreement for H. influenzae (82.0%, 75.6%, 77.6%), due mainly to culture-negative/qPCR-positive samples, indicating lower sensitivity of the culture-based methods. The lowest positive agreement (culture-positive/qPCR-positive samples) was observed for S. pneumoniae (35.1%, 71.2%, 71.2%). Bacterial load values for each species showed a proportion of culture-negative samples with a load detected by qPCR; for some samples, the loads were in line with those observed in culture-positive samples. In the NTHI-004 study, of fresh samples that tested culture-positive, less than 50% remained culture-positive when tested from freeze/thawed samples. In the NTHI-004 study, of fresh samples that tested culture-positive, less than 50% remained culture-positive when tested from freeze/thawed samples. Real-time PCR on frozen sputum samples has enhanced sensitivity and specificity over culture-based methods, supporting its use for the identification of common respiratory bacterial species in patients with COPD.