Faculty Bibliography

Introduction: Achalasia is an esophageal dysmotility disorder. Rarely, untreated achalasia can lead to massive dilatation of the esophagus causing tracheal compression and respiratory compromise. We report a case of achalasia causing acute life-threatening ventilatory failure requiring emergent bronchoscopic management. Case report: A forty-seven year old female with presumptive achalasia was admitted to an outside hospital with shortness of breath, six months of weight loss and progressive inability to tolerate oral intake. Chest CT showed a massively dilated esophagus with anterior displacement and compression of the trachea and mainstem bronchi. Two days after admission, she was allowed to eat and developed respiratory distress requiring intubation. Soon after transfer to our institution she was extubated and was without stridor. Esophagogastroduodenoscopy demonstrated an esophagus full of food and inability to pass the endoscope into the stomach. A liquid diet was recommended but the patient continued to eat solids. Several days later the patient vomited, aspirated and developed respiratory distress. She was found to have a pH of 6.86, pCO₂ of 193mmHg and pO₂ of 87mmHg. Airway examination demonstrated diffuse neck enlargement and during direct laryngoscopy only the epiglottis could be visualized. An endotracheal (ET) tube was placed and secured at 20cm at the incisors. However ventilation was nearly impossible with high inspiratory pressures, minimal tidal volume and extremely prolonged exhalation. Bronchoscopy revealed severe extrinsic compression of the trachea and mainstem bronchi (figure 1) causing occlusion of the trachea below the level of the ET tube. The ET tube was advanced to 1cm above the carina with normalization of airway pressures. Several hours later desaturation occurred and clinical exam as well as chest radiograph revealed right mainstem intubation. Bronchoscopy was again performed and the ET tube was placed with the tip immediately above the carina when the neck was in full flexion. Chest CT confirmed previous findings (figure 2). Discussion: There are approximately 30 reported cases of achalasia causing respiratory compromise due to tracheal compression and only a handful of these required intubation for respiratory failure. This case is unique in that the dilated esophagus caused anterior displacement of the larynx, complicating laryngoscopy, and compression of almost the entire trachea, requiring bronchoscopy to precisely place the ET tube to stent open the airway to permit ventilation. This case highlights that achalasia is a possible cause of extrinsic laryngeal, tracheal and bronchial compression whose management may be optimized using fiberoptic bronchoscopy. (Figure Presented)

INTRODUCTION: The incidence of asthma may be increased in patients with obesity. However, recognition of airway disease is confounded by abnormal lung physiology seen in obesity per se. Healthy obese patients with normal spirometry have elevated resistance (oscillometry) similar to non-obese patients with obstructive spirometry. However, in obese patients elevated resistance is associated with decreased FRC (mass loading), whereas FRC is normal-high in non-obese patients with airway obstruction. We hypothesize that obese patients with obstructive dysfunction can be distinguished from obese patients without airway disease by relating oscillometry findings to resting lung volume (FRC). METHODS: 183 obese subjects (BMI 30-73 kg/m²) were divided into 3 groups. Group 1: healthy obese (non-smoker, no history of lung disease, normal FEV₁/FVC; n= 62) Group 2: obstructive airway disease (reduced FEV₁/FVC; n= 40) Group 3: reported diagnosis of asthma with normal airflow (normal FEV₁/FVC; n= 81). All subjects underwent spirometry and plethysmography. Oscillometry was performed at baseline and repeated during voluntary inflation to predicted FRC to minimize the confounding effect of reduced lung volume on airway resistance. Oscillometry parameters included resistance at 5 and 20Hx (R₅, R₂₀). RESULTS: VC, IC, and ERV were similar in Groups 1 and 2 (Table 1). FRC was reduced in all subjects of Group 1; in Group 2 higher values were seen extending into normal range despite obesity. R₅ and R₂₀ were elevated in all subjects to a similar degree in Groups 1 and 2; calculation of specific conductance for R₅ and R₂₀ (SGrs5, SGrs20) distinguished Group 1 from Group 2. Based on these observations, Group 3 was divided into normal vs. reduced FRC (Table 2). To minimize the effect of lung volume on resistance in Group 3, oscillometry data were analyzed at similar lung volumes (i.e. during voluntary inflation in subjects with reduced FRC vs. at baseline in remaining subjects with normal FRC). Subjects with normal FRC demonstrated higher values for R₅ and R₂₀ compared to subjects with reduced FRC. Response to bronchodilator was only noted in those subjects with normal FRC. CONCLUSIONS: Preservation of FRC occurred in obese patients with known airway disease and reduced FEV₁/FVC. In patients with normal airflow despite self reported asthma, increased airway resistance was associated with normal FRC. Therefore, whereas a reduction in FRC is expected in healthy obese subjects, a normal FRC may reflect pseudo-normalization as a manifestation of airway disease even when FEV₁/FVC is normal. (Table Presented)

RATIONALE: Residents and area workers who inhaled dust and fumes from the World Trade Center disaster reported lower respiratory symptoms in two World Trade Center Health Registry surveys (2003-2004 and 2006-2007), but lung function data were lacking. OBJECTIVES: To examine the relationship between persistent respiratory symptoms and pulmonary function in a nested case-control study of exposed adult residents and area workers 7-8 years post-9/11/2001. METHODS: Registrants reporting post-9/11 onset of a lower respiratory symptom in the first survey and the same symptom in the second survey were solicited as potential cases. Registrants without lower respiratory symptoms in either Registry survey were solicited as potential controls. Final case-control status was determined by lower respiratory symptoms at a third interview (the study), when spirometry and impulse oscillometry were also performed. MAIN RESULTS: We identified 180 cases and 473 controls. Cases were more likely than controls to have abnormal spirometry (19% versus 11%, P<0.05), and impulse oscillometry measurements of elevated airway resistance, R5 (68% versus 27%, P<0.0001) and frequency dependence of resistance, R5-20 (36% versus 7%, P<0.0001). When spirometry was normal, cases were more likely than controls to have elevated R5 and R5-20 (62% versus 25% and 27% versus 6% respectively, both P<0.0001). Associations between symptoms and oscillometry held when factors significant in bivariate comparisons (BMI, spirometry, exposures) were analyzed using logistic regression. CONCLUSIONS: This study links persistent respiratory symptoms and oscillometric abnormalities in WTC-exposed residents and area workers. Elevated R5 and R5-20 in cases despite normal spirometry suggested distal airway dysfunction as a mechanism for symptoms

OBJECTIVE: : To describe pathologic findings in symptomatic World Trade Center-exposed local workers, residents, and cleanup workers enrolled in a treatment program. METHODS: : Twelve patients underwent surgical lung biopsy for suspected interstitial lung disease (group 1, n = 6) or abnormal pulmonary function tests (group 2, n = 6). High-resolution computed axial tomography and pathologic findings were coded. Scanning electron microscopy with energy-dispersive x-ray spectroscopy was performed. RESULTS: : High-resolution computed axial tomography showed reticular findings (group 1) or normal or airway-related findings (group 2). Pulmonary function tests were predominantly restrictive. Interstitial fibrosis, emphysematous change, and small airway abnormalities were seen. All cases had opaque and birefringent particles within macrophages, and examined particles contained silica, aluminum silicates, titanium dioxide, talc, and metals. CONCLUSIONS: : In symptomatic World Trade Center-exposed individuals, pathologic findings suggest a common exposure resulting in alveolar loss and a diverse response to injury

There is an increasing awareness of the role of distal airways in the pathophysiology of obstructive lung diseases including asthma and chronic obstructive pulmonary disease. We hypothesize that during induced bronchoconstriction: 1) disparity between distal and proximal airway reactivity may occur; and 2) changes in distal airway function may explain symptom onset in subjects with minimal FEV(1) change. 185 subjects underwent methacholine challenge testing (MCT). In addition to spirometry, oscillometry was performed at baseline and after maximum dose of methacholine; 33/185 also underwent oscillometry after each dose. Oscillometric parameters included resistance at 5 and 20 Hz (R(5,) R(20)) and heterogeneity of distal airway mechanics assessed by frequency dependence of resistance 5-20 Hz (R(5-20)) and reactance area (AX). R(5) varied widely during MCT (range -0.8 - 11.3 cmH(2)O/L/s) and correlated poorly with change in FEV(1) (r = 0.17). Changes in R(5) reflected changes in both R(20) and R(5-20) (r = 0.59, p<0.05; r = 0.87, p<0.0001). However, R(20) increased only 0.3 cmH(2)O/L/s, while R(5-20) increased 0.7 cmH(2)O/L/s for every 1cmH(2)O/L/s change in R(5,) indicating predominant effect of distal airway mechanics. 9/33 subjects developed symptoms despite minimal FEV(1) change (<5%), while R(5) increased 42% due to increased distal airway heterogeneity. These data indicate disparate behavior of proximal airway resistance (FEV(1) and R(20)) and distal airway heterogeneity (R(5-20) and AX). Distal airway reactivity may be associated with methacholine-induced symptoms despite absence of change in FEV(1). This study highlights the importance of disparity between proximal and distal airway behavior, which has implications in understanding pathophysiology of obstructive pulmonary diseases and their response to treatment

Background: In the 7 years after the WTC disaster, the annual number of FDNY retirements attributable to pulmonary disability increased nearly 4-fold. FDNY rescue workers evaluated for pulmonary disability at our subspecialty center were previously found to have an obstructed phenotype based on FEV₁/FVC, Methacholine Challenge Test (MCT) reactivity, or bronchodilator (BD) reactivity (59% of N=1720). In this pilot study, we examined the long-term efficacy of treatment and its effect on disease progression in a subgroup (N=450) of individuals with subspecialty pulmonary testing who were referred for disability evaluation before and after a course of treatment. Methods: Our study cohort includes individuals that were symptomatic, had subspecialty pulmonary testing (pre-treatment), and were referred for disability evaluation after a full course of treatment (post-treatment). Disability evaluations were performed 30 days after weaning from inhaled medication. Individuals were excluded if their post-treatment PFT was less than three months after starting treatment. Change in lung function over time and post treatment were analyzed (N=415). Values are presented as medians with IQR. We defined statistical significance as P<0.05 using the paired t-test. Analyses were performed using GraphPad and SPSS software. Results: Individuals evaluated by MCT presented for disability evaluation earlier, with a shorter interval of treatment (7.5 months (5-10)) compared to those that received spirometry with BD, (14.5 months (8-25) p<0.0001). FEV₁ %Pred and FEV₁/FVC declined significantly; p<0.0001. FEV₁ observed declined at a slower rate in the treatment group than in the entire WTC-exposed FDNY cohort, including those not referred for subspecialty evaluation: 15cc/year vs. 26cc/year. After treatment course, BD response was unchanged, but methacholine reactivity improved significantly; Fig. 1. (Figure presented) Airway Hyperreactivity Post-Treatment. (A): BD response did not improve from pre- to post-treatment, (N=135). Shading represents a positive BD response. (B): Methacholine reactivity significantly improved, from failing at a cumulative dose of 1.4 mg/mL to failing at a cumulative dose of 64 mg/mL (N=35). There was no difference between individuals receiving bronchodilator response and methacholine challenge in FEV1 or FEV1/FVC both pre- and post treatment, the decline FEV1 from pre- to post-Treatment, time to entry into treatment cohort, or demographics (years of service, exposure, age at 9/11, or BMI). Conclusion: Treatment with removal from fire fighting, inhaled steroids and beta agonists did not improve spirometric measures, or BD response, but slowed the rate of decline and decreased hyper-reactivity to the MCT. Improvement in reactivity defined by MCT but not defined by BD response suggests that the pathways leading to BD response and MCT reactivity may be different and may respond differently to treatment

Introduction: Airway dysfunction has been detected by oscillometry in obese subjects despite normal large airway function as assessed by spirometry. This has been attributed to lung/airway compression as reflected by reduced FRC; we previously demonstrated improvement of abnormalities towards normal upon voluntary inflation to predicted FRC (AJRCCM 2010; 181:A2532). However, other causes of airway dysfunction such as inflammation or concomitant intrinsic airway disease may coexist and could not be excluded. The present study re-evaluated these subjects following bariatric surgery induced weight loss to evaluate for residual abnormality. Methods: 22 morbidly obese subjects without history of smoking and/or cardiopulmonary disease, underwent evaluation pre/post bariatric surgery (20% reduction in weight). Spirometry, plethysmography and impulse oscillometry (IOS) were performed. IOS parameters included resistance at 5Hz (R5), resistance at 20Hz (R20) frequency dependence of resistance (R5-20) and reactance at 5Hz (X5).IOS was also performed at an elevated lung volume (~1 liter) targeted to restore FRC to predicted values. All IOS measurements were repeated post bronchodilator. Results: Baseline weight and BMI were 256+/-43 kg and 46+/-7 kg/m², respectively. All subjects lost >20% of body weight, but obesity persisted in all subjects (weight 182 kg, BMI 33 kg/ m2). FEV /FVC was normal at baseline and remained unchanged post weight loss 1 (81+/-3% vs 83+/-4%) indicating normal large airway function. FRC and ERV improved post weight loss but values remained abnormal (FRC from 60+/-12 to 77+/-21% predicted, ERV from 46+/-16 to 75+/-38% predicted, p<0.05). Although IOS parameters improved following weight loss, data remained above the upper limit of normal (R5 from 6.8+/-1.8 to 5.1+/-1.4 cmH₂O/l/s, R₂₀ from 4.7+/-1.1 to 3.9+/-0.9 cmH₂O/l/s, R_5-20 from 2.1+/-1.1 to 1.2+/-0.9 cmH_2O /l/s, X₅ from -3.2+/-1.7 to -1.8+/-0.9 cmH₂O /l/s, p<0.05). Since FRC remained abnormal following weight loss, IOS was repeated following voluntary lung inflation (FRC 142+/-30%). While R20 corrected to normal at the elevated FRC (R₂₀ 3.1+/-1.0 cmH₂ O/l/s), R5, R5-20 and X5 remained abnormal indicating residual distal airway dysfunction (R₅ 4.2+/-1.4 cmH₂O/l/s, , R_5-20 1.1+/-0.7 cmH₂O /l/s, X₅ -2.0+/-0.8 cmH₂O /l/s); these residual oscillometric abnormalities were present in 11/22 subjects. Residual airway dysfunction was demonstrated by low specific conductance (assessed at 5HZ) despite restoration of FRC to supranormal values. Conclusions: Distal airway dysfunction persisted following weight loss and was not attributable to persistent mass loading in a subgroup of patients without clinical evidence of airway disease. These abnormalities may represent either functional abnormalities due to persistent obesity and/or intrinsic airway disease

Introduction: Pulmonary function evaluation in patients with cystic fibrosis (CF) has demonstrated disparity between spirometric and oscillometric assessments. Most studies have indicated that oscillometry may appear normal despite significant abnormalities on spirometry. However, normal values for impulse oscillometry (IOS) in pediatric populations are limited and vary by study. The present study assessed the role for IOS by assessment of both the acute response to bronchodilator and the chronic response to treatment. Methods: Patients hospitalized with exacerbations of CF were evaluated with both spirometry and oscillometry. Data were obtained pre and post bronchodilator administration and related to published normative data. When feasible, lung volumes were assessed by plethysmography. Serial testing was performed during and following standard therapy which included vigorous chest physical therapy and intravenous antibiotics targeted to the predominate organism isolated from sputum or bronchoscopy specimens. Results: Data were available in 5 patients with CF with age ranging from 5 to 44 years. Abnormal spirometry was evident in 4 subjects. Although FEV₁/FVC was mildly reduced in these subjects (68+5%), the predominant abnormality was reduction in vital capacity (50+12%). HRCT demonstrated severe mucous plugging in multiple airways and bronchoscopy in one patient confirmed total occlusion of the bronchial lumen form respiratory secretions. Despite these spirometric and radiographic abnormalities, oscillometric assessment of resistance assessed was within published normal limits in these subjects. However, a positive response to bronchodilator was observed in 3 patients and serial testing in one subject demonstrated further improvement in airway resistance by IOS. These changes in oscillometric data occurred with minimal change in FVC and FEV₁. Conclusions: Although IOS parameters in an individual patient may be within published normal limits, reduction in resistance may be apparent either acutely post bronchodilator or chronically following treatment. These improvements in IOS parameters may not be apparent on spirometry, providing a potential role for IOS in the evaluation of patients with CF. These data suggest that improvement in post bronchodilator measurements of airway resistance may be a useful adjunct to guide the appropriate length of treatment for CF exacerbations

INTRODUCTION: Diffuse alveolar hemorrhage (DAH) is associated with a variety of clinical disorders, but is very rarely associated with post-infectious glomerulonephritis (PIGN). In fact, there have only been three cases previously reported in the literature. We describe a patient who was found to have DAH in the setting of biopsy-proven PIGN and discuss his course in comparison to prior cases. CASE PRESENTATION: A 37 year old African American man with a history of gunshot wound presented to the hospital for respiratory distress. He reported a dry cough and worsening shortness of breath over the past several days. He denied sputum production, fever, sore throat, or urinary complaints. Symptoms began following a one week history of vague gastrointestinal symptoms that spontaneously resolved. On examination, patient was afebrile with blood pressure of 160/110 mmHg, heart rate of 96 beats per minute, respiratory rate of 24 breaths per minute, and oxygen saturation 93% on room air. Pertinent findings included absence of JVD, diffuse rales and ronchi, normal S1 and S2 without murmurs or gallops, and absence of peripheral edema. Serum creatinine was 1.1 mg/dL and hemoglobin 9.5 g/dL. Chest radiograph revealed diffuse bilateral infiltrates; computed tomography of chest revealed dense multifocal infiltrates of unclear etiology. Urine analysis revealed large proteinuria and hematuria. The patient was empirically treated for pneumonia; however, his pulmonary status worsened, as did his renal function. A pulmonary-renal syndrome was considered; anti-glomerular basement membrane, antinuclear, antineutrophil cytoplasmic, and anti-ds DNA antibodies were negative. Cryoglobulin and HIV testing was negative. His antistreptolysin antibody titer was extremely elevated at 997 IU/mL, with low C3 and normal C4 levels. Bronchoscopy with serial bronchoalveolar lavages produced increasing red blood cell counts and hemosiderin-laden macrophages. A renal biopsy revealed granular deposition in mesangium and glomerular basement membrane that stained positive for C3 by immunofluorescence. Light microscopy revealed margination of neutrophils in capillary lumina, also consistent with postinfectious glomerulonephritis. The patient was treated with pulse dosing of high dose intravenous methylprednisolone. His respiratory status and hypoxia improved, as did his renal function. DISCUSSION: DAH has previously been associated with an array of clinical diagnoses, some of which concomitantly affect the kidney, specifically acute nephritides. PIGN's association with DAH is extremely rare with only 3 cases reported in the medical literature and the evidence for a treatment strategy is subsequently nonexistent. PIGN characteristically develops ten to fourteen days after pharyngitis or skin infection with group A beta-hemolytic streptococcus. PIGN clinically manifests as gross hematuria, oliguric renal failure, edema, and hypertension. Laboratory studies usually reveal an elevated antistreptolysin antibody titer and a low C3 level along with a normal C4 level. The clinical course for PIGN is usually very mild, as was the case for our patient. Proposed pathogenic mechanisms for the development of DAH with PIGN are not well founded, but include immune complex deposition on broncho-alveolar epithelium and capillary basement membrane. An acute inflammatory reaction may disrupt the alveolar bed and capillary basement membrane, and lead to capillaritis and DAH. In the few cases reported, high dose intravenous pulse steroid therapy was used with consistent improvement in DAH and intermittent resolution of renal dysfunction; one of the previously reported cases did progress to renal failure. CONCLUSIONS: Diffuse alveolar hemorrhage is very rarely associated with postinfectious glomerulonephritis; however, a clinician must be aware of this possibility once the appropriate constellation of symptoms exists. An accurate diagnosis must be made for the purposes of treatment and prognosis

INTRODUCTION: Endotracheal intubation is associated with complications that include laryngeal edema, ulceration, and glottic/subglottic granulation tissue formation. Such traumatic consequences can lead to respiratory difficulties. Here we report a unique case of traumatic intubation leading not only to respiratory difficulties while awake, but during sleep as well in the form of sleep disordered breathing. CASE PRESENTATION: A 53 year old female smoker presented with syncope. Cardiac and neurological evaluation were normal. Upon further interview she reported excessive daytime somnolence, and a necessity to sleep sitting completely upright. Past medical history was notable for tracheostomy and subsequent decannulation after laryngeal fracture from a motor vehicle accident during childhood. Three years ago she required blind intubation while undergoing breast lumpectomy. The patient was extubated following the surgery, however, she was not spontaneously breathing. Emergent re-intubation was attempted unsuccessfully, and emergent cricothyroidotomy was required. Computed tomography (CT) of the neck post cricothyroidotomy displayed an edematous epiglottis. Treatment with corticosteroids was initiated and decannulation was performed 2 weeks later. Currently, physical examination revealed a normal body weight. The orophraynx was clear without palpable masses. There was a well healed tracheostomy scar, and of note, an inspiratory stridor was audible. Spirometry was performed, and revealed reduced inspiratory airflow with a visible plateau and flow oscillations, indicating a variable extrathoracic upper airway obstruction (Figure A). Nocturnal polysomnogram was performed to evaluate the daytime somnolence and revealed a plateau on the inspiratory airflow waveform with snoring indicating inspiratory flow limitation (Figure B). She was started on continuous positive airway pressure (CPAP) therapy to overcome the obstruction to airflow. Direct laryngoscopy was performed revealing redundant floppy supraglottic aryepiglottic mucosal fold with fluttering during respiration (Video), providing an etiology for the upper airway obstruction noted on both spirometry and nocturnal polysomnography. Supraglottoplasty was performed to remove the redundant tissue, resulting in resolution of her stridor and significant symptomatic improvement in her daytime somnolence. DISCUSSION: Sleep disordered breathing (S