Michael P Habib

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Pulmonary Physiology

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Journals/Publications

• Habib, M. P., Chowdhary, S., & Budhiraja, R. (2010). Impact of Hemoglobin Levels on Outcomes in Patients on Mechanical Ventilation. Chest, 138(4), 274A. doi:10.1378/chest.10525
• Zeltser, D., Wilson, R., Westerhausen, U., Weiler, Z., Wedzicha, J. A., Watz, H., Vlastos, F., Viljoen, J., Triot, P., Toubis, M., Theron, M. S., Taminau, D., Stockley, R. A., Smith, C., Sharafkhaneh, A., Sethi, S., Schroder-babo, W., Schaberg, T., Sanchez, R. P., , Rubinstein, E., et al. (2010). Correction: Pulsed moxifloxacin for the prevention of exacerbations of chronic obstructive pulmonary disease: A randomized controlled trial [Respiratory Research, 11, (2010):(10)], DOI: 10.1186/1465-9921-11-10. Respiratory Research, 11(1). doi:10.1186/1465-9921-11-88
• Plautz, M., Piquette, C. A., Niewoehner, D. E., Kesten, S., & Habib, M. P. (2008). Premature discontinuation of patients: A potential bias in COPD clinical trials (European Respiratory Journal (2007) 30, (898-906)). European Respiratory Journal, 31(1), 226-226. doi:10.1183/09031936.50104606
• Plautz, M., Piquette, C. A., Niewoehner, D. E., Kesten, S., & Habib, M. P. (2007). Premature discontinuation of patients: a potential bias in COPD clinical trials.. The European respiratory journal, 30(5), 898-906. doi:10.1183/09031936.00104606
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  Premature discontinuation from clinical trials may bias results against effective therapies. In the present study mortality rates were retrospectively reviewed in a 6-month, randomised, placebo-controlled trial in which tiotropium 18 mug daily was shown to decrease chronic obstructive pulmonary disease exacerbations. Patients participated for 6 months even if trial medication was prematurely discontinued. Exposure-adjusted incidence rates (IRs) were calculated for randomisation-end trial, randomisation-end trial drug (0-ED) and end trial drug-end trial (ED-ET). Of 1,829 patients (forced expiratory volume in one second 1.04 L (36% predicted), mean age 68 yrs, 99% male), 16% tiotropium and 27% placebo patients prematurely stopped trial medication. The number of fatal events for the entire cohort was: 62 all cause, including 16 cardiac and 16 lower respiratory. IRs for fatal events per 100 patient-yrs were higher in the discontinued period: 1.9 (0-ED) versus 23.0 (ED-ET) in the tiotropium group and 1.8 versus 19.0 in the placebo group. Respective IRs for fatal cardiac events were 0.7 versus 2.8 (tiotropium) and 0.5 versus 6.2 (placebo); for fatal lower respiratory events were 0.7 versus 2.8 (tiotropium) and 0.8 versus 5.4 (placebo). Rate ratios (tiotropium/placebo) for fatal events were lower in the discontinued period: 1.4 versus 0.5 for cardiac and 0.9 versus 0.5 for lower respiratory. Higher incidence rates of fatal events occurred following premature discontinuation of study medication. Incomplete information from rate ratios occurs as a result of failure to consider outcomes of patients who discontinue early from clinical trials.
• Plautz, M., Piquette, C. A., Niewoehner, D. E., Kesten, S., & Habib, M. P. (2006). PREMATURE DISCONTINUATION OF PATIENTS MOST AFFECTED BY THE DISEASE UNDER STUDY: A POTENTIAL BIAS IN COPD CLINICAL TRIALS. Chest, 130(4), 179S. doi:10.1378/chest.130.4_meetingabstracts.179s-a
• Young, S. L., Wittes, J., O'connor, T. Z., Nichol, K. L., Neuzil, K. M., Habib, M. P., & Gorse, G. J. (2006). Impact of a winter respiratory virus season on patients with COPD and association with influenza vaccination.. Chest, 130(4), 1109-16. doi:10.1378/chest.130.4.1109
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  We assessed the effects of an influenza season on patients with COPD. Data from 2,215 veterans in a multicenter, randomized, double-blind influenza vaccine efficacy study were analyzed for changes in spirometric and functional status, comparing patients with laboratory-documented influenza (LDI)-caused illness, non-LDI-caused respiratory illness, or no illness, and for association with influenza vaccination..Patients received either IM trivalent inactivated influenza virus vaccine (TIV) plus intranasal trivalent, live attenuated, cold-adapted influenza virus vaccine (TC) or TIV plus intranasal placebo (TP). We performed spirometry, measured the chronic lung disease severity index (CLDSI) score to assess functional status and well-being, and tested for influenza virus infection..Worsening in FEV(1), percentage of predicted FEV(1), and CLDSI score (p < 0.001) was associated with acute respiratory illness in 585 illnesses including 94 LDI-caused illnesses. LDI-caused illness was more likely to be associated with worsening in FEV(1) and CLDSI score acutely than non-LDI-caused illness (p < 0.01). Logistic regression showed acute respiratory illness (odds ratio [OR], 1.78; 95% confidence limit [CL], 1.40 to 2.26) to be associated with worsening in CLDSI score, and receipt of TC (OR, 1.39; 95% CL, 1.10 to 1.74) and no illness (OR, 0.70; 95% CL, 0.53 to 0.91 for acute respiratory illness) to be associated with better CLDSI score at the end of the study. Hospitalization was more frequent in patients with acute respiratory illness (p < 0.0001)..Acute respiratory illness was associated with increased health-care utilization and obstruction to airflow, and worse functional status and well-being. At the end of the study, receipt of TC was associated with improvement and acute respiratory illness was associated with worsening in functional status and well-being.
• Habib, M. P., & Campbell, S. C. (2005). SEROLOGIC STUDIES IN PATIENTS WITH PULMONARY COCCIDIOIDAL NODULES OR MASSES. Chest, 128(4), 185S. doi:10.1378/chest.128.4_meetingabstracts.185s
• Haniuda, M., Robbins, R. A., Numanami, H., Nelson, D. K., Koyama, S., Hoyt, J. C., Habib, M. P., Freels, J. L., & Amano, J. (2003). Peroxynitrite enhances interleukin-10 reduction in the release of neutrophil chemotactic activity.. American journal of respiratory cell and molecular biology, 29(2), 239-44. doi:10.1165/rcmb.2002-0275oc
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  Peroxynitrite, formed by nitric oxide and superoxide, has been shown to nitrate and reduce the function of proinflammatory proteins such as interleukin (IL)-8, monocyte chemoattractant protein-1, and eotaxin, but in contrast, to enhance the function of the anti-inflammatory cytokine IL-10 in reducing IL-1 release from blood monocytes. However, the effect of nitrated IL-10 on release of proinflammatory cytokines from lung epithelial cells is unknown. We hypothesized that peroxynitrite would enhance the capacity of human IL-10 to reduce inflammatory mediators released by epithelial cells. To test this hypothesis, recombinant human IL-10 was evaluated for its capacity to attenuate the release of neutrophil chemotactic activity and IL-8 from a human epithelial cell line in response to IL-1 beta and tumor necrosis factor-alpha. Neutrophil chemotactic activity and IL-8 in lung epithelial culture supernatant fluids were significantly lower after culture with nitrated human IL-10 compared with non-nitrated human IL-10 controls (P < 0.05). Consistent with these results, nitrated human IL-10 attenuated IL-8 mRNA expression more than non-nitrated human IL-10 controls (P < 0.05). These data demonstrate that peroxynitrite exposed human IL-10 has enhanced anti-inflammatory activity and suggest that nitration may play a critical role in the regulation of inflammation within the lower respiratory tract.
• Haniuda, M., Sato, E., Robbins, R. A., Numanami, H., Nelson, D. K., Koyama, S., Hoyt, J. C., Habib, M. P., & Freels, J. L. (2003). Serine protease inhibitors modulate chemotactic cytokine production by human lung fibroblasts in vitro.. American journal of physiology. Lung cellular and molecular physiology, 284(5), L882-90. doi:10.1152/ajplung.00211.2002
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  Chemotactic chemokines can be released from lung fibroblasts in response to interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha. An imbalance between proteases and antiproteases has been observed at inflammatory sites, and, therefore, protease inhibitors might modulate fibroblast release of chemotactic cytokines. To test this hypothesis, serine protease inhibitors (FK-706, alpha(1)-antitrypsin, or N(alpha)-p-tosyl-L-lysine chloromethyl ketone) were evaluated for their capacity to attenuate the release of neutrophil chemotactic activity (NCA) or monocyte chemotactic activity (MCA) from human fetal lung fibroblasts (HFL-1). Similarly, the release of the chemoattractants IL-8, granulocyte colony-stimulating factor, monocyte chemoattractant protein-1, macrophage colony-stimulating factor, and granulocyte/macrophage colony-stimulating factor, from HFL-1, were evaluated in response to IL-1beta and TNF-alpha. NCA, MCA, and chemotactic cytokines were attenuated by FK-706. However, matrix metalloproteinase inhibitors were without effect, and cysteine protease inhibitors only slightly attenuated chemotactic or cytokine release. These data suggest that IL-1beta and TNF-alpha may stimulate lung fibroblasts to release NCA and MCA by a protease-dependent mechanism and that serine protease inhibitors may attenuate the release.
• Haniuda, M., Sato, E., Robbins, R. A., Numanami, H., Nelson, D. K., Koyama, S., Hoyt, J. C., Habib, M. P., Freels, J. L., & Amano, J. (2003). Serine protease inhibitors modulate smoke-induced chemokine release from human lung fibroblasts.. American journal of respiratory cell and molecular biology, 29(5), 613-9. doi:10.1165/rcmb.2003-0113oc
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  Smoking is associated with lung inflammation and a protease-antiprotease imbalance. We previously reported that cigarette smoke extract (CSE) stimulates human lung fibroblasts to release chemotactic cytokines. We hypothesized that serine protease inhibitors might modulate lung fibroblast release of chemotactic cytokines in response to CSE. To test this hypothesis, serine protease inhibitors (FK706, alpha1-antitrypsin, methoxysuccinyl-Ala-Ala-Pro-Val chloromethyl ketone, or Nalpha-p-tosyl-L-lysine chloromethyl ketone) were evaluated for their capacity to attenuate the release of neutrophil chemotactic activity (NCA) and monocyte chemotactic activity (MCA) from human fetal lung fibroblasts by the blind-well chemotactic chamber. Metalloproteinases and cysteine proteinases were not examined in this study. Similarly, the release and gene expression of chemokines and nuclear factor-kappaB (NF-kappaB) activation were measured by means of enzyme-linked immunosorbent assay and reverse transcriptase-polymerase chain reaction. Release of NCA, MCA, chemotactic chemokines including interleukin-8, granulocyte colony-stimulating factor, monocyte chemoattractant protein-1, and granulocyte-macrophage colony-stimulating factor, and the expression of interleukin-8 and monocyte chemoattractant protein-1 mRNA were attenuated by FK706. Furthermore, FK706 suppressed NF-kappaB activation. These data suggest that serine protease inhibitors attenuate the CSE-induced release of NCA and MCA from human fetal lung fibroblasts and that the inhibitory action of antiproteases might depend on NF-kappaB signaling pathway.
• Springall, D. R., Robbins, R. A., Polak, J. M., Hoyt, J. C., Habib, M. P., Buttery, L. D., & Barnes, P. J. (2003). Cigarette smoke decreases inducible nitric oxide synthase in lung epithelial cells.. Experimental lung research, 29(1), 17-28. doi:10.1080/01902140303759
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  Cigarette smoking has been associated with decreased exhaled nitric oxide (NO). To investigate the mechanism of this decrease, the effects of a cigarette smoke extract were evaluated a murine lung epithelial cell line (LA-4), a human lung epithelial cell line (A549), and primary cultures of human lung epithelial cells induced to produce NO by cytokines. NO production was evaluated by measuring nitrite, a stable end product of NO, in cell culture supernatant fluids. Cigarette smoke extract caused a reduction in the cytokine-induced nitrite concentrations in the culture supernatant fluids from all 3 cell types (P < .01, all comparisons). To further investigate these observations, immunohistochemistry demonstrated a decrease in cytokine-induced inducible NO synthase (iNOS) protein expression and iNOS mRNA after cigarette smoke extract exposure in LA-4 cells. However, iNOS mRNA half-life was not altered by the smoke extract, suggesting that the smoke extract decreased NO by decreasing iNOS mRNA transcription. These findings demonstrate that cigarette smoke extract decreases iNOS expression and NO production from lung epithelial cells.
• Zadeikis, N., Xiang, J. X., Wunderink, R. G., Wiesinger, B. A., Tennenberg, A. M., Smith, L. G., Khashab, M. M., Kahn, J. B., Habib, M. P., & Dunbar, L. M. (2003). High-dose, short-course levofloxacin for community-acquired pneumonia: a new treatment paradigm.. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 37(6), 752-60. doi:10.1086/377539
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  Levofloxacin demonstrates concentration-dependent bactericidal activity most closely related to the pharmacodynamic parameters of the ratio of area under the concentration-time curve (AUC) to minimum inhibitory concentration (MIC) and the ratio of peak plasma concentration (C(max)) to MIC. Increasing the dose of levofloxacin to 750 mg exploits these parameters by increasing peak drug concentrations, allowing for a shorter course of treatment without diminishing therapeutic benefit. This was demonstrated in a multicenter, randomized, double-blind investigation that compared levofloxacin dosages of 750 mg per day for 5 days with 500 mg per day for 10 days for the treatment of mild to severe community-acquired pneumonia (CAP). In the clinically evaluable population, the clinical success rates were 92.4% (183 of 198 persons) for the 750-mg group and 91.1% (175 of 192 persons) for the 500-mg group (95% confidence interval, -7.0 to 4.4). Microbiologic eradication rates were 93.2% and 92.4% in the 750-mg and 500-mg groups, respectively. These data demonstrate that 750 mg of levofloxacin per day for 5 days is at least as effective as 500 mg per day for 10 days for treatment of mild-to-severe CAP.
• Zadeikis, N., Xiang, J., Wunderink, R. G., Wiesinger, B. A., Tenneberg, A. M., Smith, L. G., Khashab, M. M., Kahn, J. B., Habib, M. P., & Dunbar, L. M. (2003). Erratum: High-dose, short-course levofloxacin for community-acquired pneumonia: A new treatment paradigm (Clinical Infectious Diseases (2003) 37 (752-60)). Clinical Infectious Diseases, 37(8), 1147-1147. doi:10.1086/379736
• Habib, M. P. (2001). Management of clinical failures in non-ICU patients with chronic obstructive pulmonary disease exacerbations.. Chemotherapy, 47 Suppl 4(Suppl. 4), 39-46; discussion 53-4. doi:10.1159/000049179
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  Clinical failure after initial treatment for exacerbations of chronic obstructive pulmonary disease (COPD) occurs in 10-25% of cases. Once the original diagnosis is confirmed, there is a need to optimise therapy, including introducing bronchodilators and corticosteroids. The use of aggressive antibiotic treatment is recommended for patients with risk factors (elderly, more than four exacerbations per year, underlying cardiopulmonary disease) and more severe disease. Fluoroquinolones are a good choice for those patients who failed initial therapy and who require antimicrobials, including those with simple exacerbations, complicated cases with comorbidity, or those with bronchiectasis. Consideration of less common pathogens, such as Pseudomonas aeruginosa infection, should also be considered. Bacteria usually associated with exacerbations are becoming increasingly resistant, and this needs to be considered when deciding on appropriate antibiotic treatment.
• Habib, M. P. (2000). Ethane as a marker of lipid peroxidation. Respiratory Research, 2(1), 1-1. doi:10.1186/rr-2001-68574
• Habib, M. P. (2000). Free radical production and diaphragm function in emphysema. Respiratory Research, 2(1). doi:10.1186/rr-2001-68583
• Tank, L. J., Lane, L. C., Habib, M. P., & Garewal, H. S. (1999). Effect of vitamin E on exhaled ethane in cigarette smokers.. Chest, 115(3), 684-90. doi:10.1378/chest.115.3.684
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  We hypothesized that micronutrient antioxidant intake may be one factor determining the development of significant COPD. Vitamin E was administered to smokers to determine if exhaled ethane was reduced and if ethane correlated with measures of lung function..Longitudinal placebo lead-in trial with posttreatment observation period..Tucson Veterans Affairs Medical Center..Twenty-nine current stable smokers having no interest in smoking cessation..Spirometry, exhaled breath ethane measurements, and vitamin E and [-carotene plasma levels followed by 3 weeks of placebo with repeat plasma vitamin levels and ethane measurements; next, 3 weeks of vitamin E (dl-a-tocopherol), 400 IU po bid followed by plasma vitamin levels and breath ethane measurements; finally, 3 weeks without vitamins followed by breath ethane and plasma vitamin levels..Vitamin E treatment did not reduce ethane significantly. Exhaled ethane levels (mean + SD: pm/min/kg) were as follows: baseline, 7.39 + 5.39; after run-in period, 6.86 + 4.09; after vitamin E, 6.36+/-3.02; and final, 7.23+/-4.63. After vitamin E therapy, a significant negative correlation existed between exhaled ethane and FEV1/FVC. Pack-years of smoking at baseline and after vitamin E were significantly associated with ethane exhaled. Initial lung function was not significantly negatively associated with vitamin E-induced changes in exhaled ethane but a negative trend was found..Vitamin E alone, unlike the combination of vitamins C, E, and beta-carotene, failed to reduced exhaled ethane in cigarette smokers. Exhaled ethane was correlated with pack-years of smoking. Smokers whose ethane values were found to fall the most tended to have better preserved lung function.
• Peng, Y. M., Habib, M. P., Garewal, H. S., Do, B. K., & Clements, N. C. (1996). Exhaled ethane and antioxidant vitamin supplements in active smokers.. Chest, 110(1), 159-64. doi:10.1378/chest.110.1.159
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  To determine the effect of nutritional agents on lipid peroxidation, 10 smokers were given 6 mg beta carotene, 200 IU vitamin E, and 250 mg vitamin C 4 times daily for 3 weeks. Lipid peroxidation was assessed by measuring baseline and postsupplementation levels of exhaled ethane. There was a 29% decrease in mean (+/-SD) exhaled ethane (4.06 +/- 1.49 vs 2.90 +/- 1.29 pmol.kg-1.min-1), with individual levels decreasing in 8 of the 10 smokers (p < 0.05, Wilcoxon sign rank test). Three nonsmokers had very low baseline levels of ethane that did not change with supplementation. Ethane production correlated with active (packs per day) and lifelong (pack-years) tobacco consumption. Also, a strong correlation was found between the decline in ethane output after micronutrient supplementation and the presupplement FEV1. Therefore, antioxidant vitamin supplementation resulted in attenuation of smoking-related lipid peroxidation, and the decreases in ethane production appears to be associated with preserved lung function.
• Habib, M. P., & Clements, N. C. (1995). Effects of low-dose hydrogen peroxide in the isolated perfused rat lung.. Experimental lung research, 21(1), 95-112. doi:10.3109/01902149509031747
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  Isolated perfused rat lungs (IPRL) were used to determine if treatment with hydrogen peroxide would result in measurable changes in exhaled ethane during the early stages of capillary leak. Pulmonary capillary filtration coefficient, pulmonary vascular resistance, and dynamic pulmonary compliance were measured at two time points in an IPRL. Additionally, exhaled ethane was determined before and after the addition of 0.25 mM H2O2 to the perfusate in a second group of lungs. Lung wet/dry weight ratios were measured at the termination of the experiments. The ethane in the exhaled alveolar gas from IPRLs ventilated with 5%CO2/20%O2/balance N2 was quantitated using gas chromatography before and after the addition of 0.25 mM H2O2 to Krebs Ringer's 5% albumin perfusate. H2O2 (0.25 mM) caused a small but significant increase in capillary filtration coefficient from 0.0122 (+/- 0.0008) to 0.0173 (+/- 0.0013) mL/min/cm H2O/g dry lung weight (p < .05). Wet/dry lung weight ratios were increased in the H2O2-treated lungs (6.0654 +/- 0.1024 versus 5.4149 +/- 0.1143; p < .05). Exhaled ethane did not increase over the period of time hydrogen peroxide was present in the perfusate. In other experiments in closed-chested rats, 0.25 mM peroxide did not cause increased exhaled ethane, whereas 1 mM H2O2 did. This latter increase in ethane was not noted in similarly perfused open-chested rats. These data indicate that small amounts of H2O2 may increase pulmonary capillary permeability without affecting exhaled ethane measurements.
• Habib, M. P., & Clements, N. C. (1995). The Early Pattern of Conjugated Dienes in Liver and Lung after Endotoxin Exposure. American Journal of Respiratory and Critical Care Medicine, 151(3_pt_1), 780-784. doi:10.1164/ajrccm/151.3_pt_1.780
• Habib, M. P., Garewal, H. S., & Clements, N. C. (1995). Cigarette smoking and ethane exhalation in humans.. American journal of respiratory and critical care medicine, 151(5), 1368-72. doi:10.1164/ajrccm.151.5.7735586
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  The time course of exhaled ethane gas was determined in the alveolar expirate of healthy, fasting smokers and nonsmokers after smoking a cigarette. Baseline ethane was measured by gas chromatography and corrected for background ethane after a 2-min washout using purified air. Ethane was measured immediately after smoking and hourly thereafter. Ethane was highest immediately after smoking, reflecting ethane in cigarette smoke. An exponential decline of ethane in smokers returned ethane to baseline within 3 h. Ethane in nonsmokers also peaked immediately after smoking but returned to baseline by 1 h. Ethane from smokers, measured 3 h after the last cigarette, was compared with ethane from healthy ex-smokers and nonsmokers. Mean (+/- SEM) baseline ethane in smokers was 2.90 +/- 0.52 pmol/min/kg, 1.55 +/- 0.36 pmol/min/kg in ex-smokers and 1.11 +/- 0.26 pmol/min/kg in nonsmokers (p < 0.05). Ethane in two smokers measured before and after a week of oral beta carotene supplementation (60 mg/d) fell by 80 and 35%. We conclude that cigarette smokers have increased baseline ethane in exhaled breath compared with non-smokers. Trials with antioxidant agents are warranted to assess their ability to reduce expired ethane levels.
• Mooradian, A. D., Habib, M. P., & Dickerson, F. (1994). Effect of simple carbohydrates, casein hydrolysate, and a lipid test meal on ethane exhalation rate.. Journal of applied physiology (Bethesda, Md. : 1985), 76(3), 1119-22. doi:10.1152/jappl.1994.76.3.1119
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  To determine the potential differences in the effect of various nutrients on lipid peroxidation, the ethane exhalation (EE) rate, an index of lipid peroxidation, was measured in rats at 4 (young), 18 (intermediate age), and 24 (aged) mo of age at fasting conditions and after acute ingestion of various test meals. The EE rate (means +/- SD) after a 15-h fast was significantly reduced in 24-mo-old rats (2.45 +/- 0.44 pmol.min-1.100 g body wt-1) and 18-mo-old rats (3.51 +/- 0.55 pmol.min-1.100 g body wt-1) compared with 4-mo-old rats (4.44 +/- 0.66 pmol.min-1.100 g body wt-1; P < 0.01). The EE rate significantly increased in 4-mo-old rats after ingestion of 50% (wt/vol) dextrose (8.59 +/- 2.9 pmol.min-1.100 g body wt-1), 50% casein hydrolysate (6.77 +/- 1.23 pmol.min-1.100 g body wt-1), and 20% neutral lipid emulsion (7.33 +/- 1.96 pmol.min-1.100 g body wt-1; P < 0.01). The response of aged rats to these nutrients compared with young rats was reduced by approximately 50%. A 25% dextrose solution or a 50% solution of sucrose, fructose, maltose, or galactose did not significantly alter EE rate. It is concluded that various macronutrients have a diverse potential of inducing lipid peroxidation. The responsiveness of aged rats to meal-induced enhancement of EE and presumably lipid peroxidation is significantly reduced.
• Mooradian, A. D., Habib, M. P., & Dickerson, F. D. (1994). Effect of diabetes, insulin, and glucose load on lipid peroxidation in the rat.. Metabolism: clinical and experimental, 43(11), 1442-5. doi:10.1016/0026-0495(94)90042-6
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  Lipid peroxidative activity in rats made diabetic with streptozocin and rats made acutely hyperglycemic by intraperitoneal dextrose administration was determined by measurement of exhaled ethane during exposure in vivo to ethane-free air (EFA). Diabetic rats demonstrated increased ethane in the expired breath while breathing EFA (5.82 +/- 0.56 pmol/min/100 g) compared with control rats (4.02 +/- 0.23 pmol/min/100 g). Insulin treatment of diabetic rats attenuated the ethane produced (4.88 +/- 0.23 pmol/min/100 g). Acute hyperglycemia increased exhaled ethane to levels higher than those seen in diabetic rats (9.87 +/- 0.98 pmol/min/100 g). Saline injected intraperitoneally to control rats produced ethane levels similar to those of untreated nondiabetic controls (4.11 +/- 0.52 pmol/min/100 g). Chronic uncontrolled hyperglycemia and acute hyperglycemia are associated with increased in vivo ethane production.
• Yetskievych, T., Mooradian, A. D., Habib, M. P., & Dickerson, F. (1994). Effect of age on L-3,5,3'-triiodothyronine-induced ethane exhalation.. Journal of applied physiology (Bethesda, Md. : 1985), 77(1), 160-4. doi:10.1152/jappl.1994.77.1.160
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  The effect of age on thyroid hormone-induced lipid peroxidation in rats was determined by measuring ethane exhalation (EE) rate. The mean basal EE rates (in pmol.min-1 x 100 g-1) at room air in 25-mo-old aged rats [3.07 +/- 0.26 (SE)] and in intermediate age (18-mo-old) rats (3.42 +/- 0.18) were significantly lower than that in young (3- to 5-mo-old) rats (4.44 +/- 0.27) (P < 0.01). After 8 days of L-3,5,3'-triiodothyronine (T3) administration, EE rates in aged rats (4.10 +/- 0.25) and in intermediate-age rats (4.16 +/- 0.35) were significantly lower than that in young rats (5.61 +/- 0.36) (P < 0.01). T3-treated young rats pair-fed with aged rats for 2 wk had EE rates (5.53 +/- 0.18) comparable to ad libitum-fed young rats, although the basal rate of EE was significantly reduced with partial food restriction (4.44 +/- 0.27 vs. 3.50 +/- 0.24) (P < 0.01). These observations indicate that reduced food intake with age cannot account for the age-related changes in T3-stimulated peroxidation rate of lipids.
• Standen, J. R., Rehm, K., Newell, J. D., Knudson, R. J., Knudson, D. E., Kaltenborn, W. T., & Habib, M. P. (1991). Expiratory computed tomography for assessment of suspected pulmonary emphysema.. Chest, 99(6), 1357-66. doi:10.1378/chest.99.6.1357
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  Results of computed tomography of the lung performed at two levels in upper lung zones at full inspiration and full expiration were compared with results of tests of ventilatory function, lung mechanics, and single breath carbon monoxide diffusing capacity in 64 subjects, many of whom had some form of airflow obstruction. From the CT scans, the mean percentage of pixels in the range -900 to -1,024 Hounsfield units, or pixel index, was determined for each subject. The highest correlations of pixel index with physiologic variables consistent with a diagnosis of emphysema were observed for CT taken at full expiration. In some subjects, the inspiratory CT would give a "false positive" for emphysema when the hyperaeration observed at inspiration was not observed at expiration. We believe that the CT scan taken at full expiration can effectively reveal the abnormal permanent enlargement of airspaces which defines emphysema and provides a noninvasive method of assessing lung morphology in the living human subject.
• Mooradian, A. D., Habib, M. P., & Dickerson, F. D. (1990). Ethane production rate in vivo is reduced with dietary restriction.. Journal of applied physiology (Bethesda, Md. : 1985), 68(6), 2588-90. doi:10.1152/jappl.1990.68.6.2588
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  Dietary restriction without malnutrition prolongs life and has a beneficial effect on age-related diseases and metabolic derangements. To test the effect of food restriction on ethane production rate, ethane exhalation was measured in rats with partial food restriction. Ethane production rate in room air in rats fed 60% of food consumed by ad libitum-fed animals for 2 wk was significantly reduced (3.50 +/- 0.25 vs. 5.21 +/- 0.34 pmol.min-1.100 g body wt-1, P less than 0.01). In 100% oxygen, ethane production in food-restricted rats was not different from that of ad libitum-fed rats (21.81 +/- 1.25 vs. 19.57 +/- 1.89 pmol.min-1.100 g-1). Fifteen hours of fasting compared with ad libitum feeding reduced ethane production modestly in room air (4.37 +/- 0.45 vs. 5.21 +/- 0.34 pmol.min-1.100 g-1) and more significantly in 100% oxygen (12.37 +/- 0.78 vs. 19.57 +/- 1.89 pmol.min-1.100 g-1). Thus, in 100% oxygen, 15 h of fasting, compared with ad libitum feeding, resulted in an approximately 40% decrease in ethane production rate. It is concluded that short-term food restriction significantly reduces ethane exhalation rate in rats when measured in room air.
• Habib, M. P. (1989). Physiologic implications of artificial airways.. Chest, 96(1), 180-4. doi:10.1378/chest.96.1.180
• Katz, M. A., & Habib, M. P. (1989). Ethane production rates and minute ventilation.. Journal of applied physiology (Bethesda, Md. : 1985), 66(3), 1264-7. doi:10.1152/jappl.1989.66.3.1264
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  Ethane quantitated in the expired alveolar gas is a noninvasive measure of free radical activity. This method has been criticized for lack of control of minute ventilation (VE) in spontaneously breathing animals, although ethane, which is poorly soluble in tissues, should not be affected by changes in VE. We measured ethane elimination rates in six strain 13 guinea pigs (GP13) during spontaneous room air breathing and in six room air breathing, pentobarbital-anesthetized, tracheostomized, externally warmed, mechanically ventilated GP13s at various levels of VE. In the ventilated animals, weight0.75/VE (metabolic activity corrected for VE) was a linear function of arterial CO2 tension (PaCO2) drawn from arterial line (r = 0.72, P less than 0.005). However, weight0.75/VE did not correlate with ethane elimination rates (r = 0.12, not significant). The mean (+/- SD) ethane elimination rates in the spontaneously breathing animals was 3.15 +/- 0.96 pmol.min-1.100 g-1 and was not significantly different from the mean rate in the mechanically ventilated animals (3.11 +/- 1.37) over a range of VE's. These data demonstrate that ethane elimination rates are not affected by changes in VE and are unaffected by pentobarbital anesthesia.
• Katz, M. A., & Habib, M. P. (1989). Source of ethane in expirate of rats ventilated with 100% oxygen.. Journal of applied physiology (Bethesda, Md. : 1985), 66(3), 1268-72. doi:10.1152/jappl.1989.66.3.1268
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  Ethane in alveolar expirate may have its source in organs other than the lung and be transported to the lung for elimination. We determined ethane production rates in rats (group I) ventilated with hydrocarbon-free air (HFA) before and after exsanguination. To determine whether the lung is the source of increased ethane production during exposure to 100% O2, we measured ethane in the expirate of nine exsanguinated, Sprague-Dawley rats (group II) mechanically ventilated with HFA and then with 100% O2. In all nine animals, ethane elimination rates on 100% O2 increased compared with HFA values. In five of the nine rats, HFA ventilation was reinstated after O2 (group III). In all five, ethane elimination fell with HFA ventilation compared with the value on 100%. Six rats with circulation intact were ventilated with HFA and then 100% O2 (group IV). Ethane production rate for group IV animals breathing HFA was not significantly different from the exsanguinated animals in group II while ventilated with HFA. The mean increase in ethane production for the group II animals was not significantly different from the group IV animals. Lung slices from four other rats (group V) were incubated in saline at 37 degrees C with FeCl2 (10 mg) added to enhance free radical formation. Paired lung samples from the same rat were incubated with either HFA or 100% O2. Headspace gas was analyzed chromatographically for ethane at 120 min. Mean ethane in the O2 samples was higher than for HFA. Rat lung tissue is the main source of increased ethane production during 100% O2 exposure.
• Shon, B. Y., Habib, M. P., Fiastro, J. F., & Campbell, S. C. (1989). Comparison of Standard Weaning Parameters and the Mechanical Work of Breathing in Mechanically Ventilated Patients. Survey of Anesthesiology, 33(2), 93. doi:10.1097/00132586-198904000-00031
• Habib, M. P., Halonen, M., Halonen, M., Sobonya, R. E., Newell, J. D., Habib, M. P., Dunn, A. M., & Baumgartener, C. C. (1988). Immunoglobulin E anaphylaxis in rabbits: mechanisms of pulmonary resistance and compliance changes.. Journal of applied physiology (Bethesda, Md. : 1985), 64(3), 1009-16. doi:10.1152/jappl.1988.64.3.1009
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  Factors causing changes in pulmonary resistance and dynamic compliance with immunoglobulin (Ig) E anaphylaxis in spontaneously breathing rabbits were assessed in ventilated rabbits using tantalum bronchography and wet-to-dry wt ratios. Ventilated rabbits demonstrated changes in resistance and compliance similar to spontaneously breathing rabbits. Chlorpheniramine pretreatment prevented increases in resistance but not decreases in compliance. Anaphylaxis constricted small (less than 1 mm) airways 20.9 +/- 16.0% (mean +/- SD) and intermediate (between 1 and 3 mm) airways 21.8 +/- 19.8%. Chlorpheniramine (10 mg/kg) prevented small airway changes and attenuated those in intermediate airways. Chlorpheniramine prevented histamine-induced constriction of small (23.6 +/- 15.7%) and intermediate (17.6 +/- 15.0%) airways. Lung wet-to-dry wt ratios were unchanged. Changes in resistance and compliance during rabbit IgE anaphylaxis are not due to changes in tidal volume or frequency. Histamine, via H1 receptors, is the principal mediator of pulmonary resistance increases but not dynamic compliance reductions. Chlorpheniramine-sensitive increases in resistance are caused by constrictions of intermediate and small airways, whereas the chlorpheniramine-resistant decrease in compliance is not caused directly by constriction of the smallest measurable airways (0.25 mm) or changes in lung water.
• Katz, M. A., Habib, M. P., & Eskelson, C. D. (1988). Ethane production rate in rats exposed to high oxygen concentration.. The American review of respiratory disease, 137(2), 341-4. doi:10.1164/ajrccm/137.2.341
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  Production rates for ethane gas, a hydrocarbon byproduct of lipid peroxidation, measured from the ethane present in the exhaled breath of rats, were used to determine changes in oxygen-free radical activity. Rates of ethane production were measured in rats housed in metabolic chambers and exposed to room air and to high oxygen concentrations. Expired ethane, adsorbed onto activated charcoal and then liberated by heating, was measured by gas chromatography. Ethane production rates in groups of 8 rats increased during 8 h of 100% oxygen exposure from a mean (+/- SE) room air value of 11.30 +/- 1.15 to 27.85 +/- 2.93 pmol/min/100 g rat (p less than 0.005). The mean (+/- SE) percent increases in ethane production after exposure to 100% oxygen in 8 rats pretreated with 0.1 mg/100 g of vitamin E in corn oil vehicle (0.1 ml/100 g) injected intraperitoneally and in a group of 5 rats injected with vehicle alone averaged 157.16 +/- 37.83% and 150.98 +/- 25.19%, respectively. The percent changes noted were not significantly different as measured by analysis of variance. These data indicate that lipid peroxidative activity, hence oxygen-free radical activity, increases in normally fed rats exposed to hyperoxia at a time prior to the previously reported neutrophil influx into the lungs of similarly exposed rats and that it is not attenuated by pretreatment with vitamin E.
• Shon, B. Y., Habib, M. P., Fiastro, J. F., & Campbell, S. C. (1988). Comparison of standard weaning parameters and the mechanical work of breathing in mechanically ventilated patients.. Chest, 94(2), 232-8. doi:10.1378/chest.94.2.232
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  Standard bedside criteria of respiratory mechanical capability and the mechanical work of spontaneous breathing were measured in 17 mechanically ventilated patients. Eleven patients were extubated within 24 hs of study and required only a brief period of mechanical ventilation (group 1). Group 2 consisted of six patients requiring more prolonged ventilator support. Group 1 patients met three of four bedside criteria; seven patients met all four. Five of six patients in group 2 also satisfied three of four standard criteria while ventilator-dependent, whereas only two patients satisfied all four when successfully weaning. As group 2 patients progressed from unsuccessful to successful weaning there was no consistent improvement in bedside criteria; however, measures of work did significantly improve. Hence, satisfaction of bedside mechanical weaning criteria is associated with weaning success in patients requiring brief mechanical ventilation. In patients requiring prolonged ventilation, work may be a better indicator of successful weaning.
• Habib, M. P., Knudson, R. J., Knudson, D. E., Klink, M. E., Kaltenborn, W. T., Habib, M. P., & Bloom, J. W. (1987). Physiologic characteristics of subjects exhibiting accelerated deterioration of ventilatory function.. The American review of respiratory disease, 136(3), 638-45. doi:10.1164/ajrccm/136.3.638
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  From a randomly selected community population sample followed with sequential surveys since 1972, 13 subjects who exhibited a mean annual decline in FEV1 greater than 60 ml/yr were drawn for detailed studies of lung function. These subjects had developed clinically significant airway obstruction during this period of follow-up. Clinical evaluation was not successful in characterizing the nature of the disorder. None of the subjects had alpha-1-antitrypsin deficiency. In a small proportion of subjects, elevated total serum immunoglobulin E may have played a role in the obstructive airway disorder. Some subjects exhibited loss of lung elastic recoil and diminished carbon monoxide diffusing capacity suggestive of developing emphysema. Others appeared to have intrinsic airway disease involving large and/or small airways, which may be fixed in some and responsive to bronchodilator in others. Thus, neither the site nor the nature of the disorder inferred from results of physiologic tests was uniform, illustrating the heterogeneous nature of chronic obstructive lung disease.
• Paquin, M. L., Hurst, P. G., Habib, M. P., Greenberg, B. R., Garewal, H. S., & Bluestein, M. (1987). Pulmonary toxicity associated with fludarabine monophosphate.. Investigational new drugs, 5(2), 207-10. doi:10.1007/bf00203548
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  Fludarabine monophosphate (FAMP), the 2-fluoro, 5' phosphate derivative of 9-beta-D-arabinofuranosyl adenine (ara-A), is a purine nucleoside antimetabolite presently undergoing clinical testing for the treatment of a variety of malignancies including lymphoproliferative disorders and acute leukemia. We report a case of diffuse interstitial pneumonitis during treatment of chronic lymphocytic leukemia with FAMP. This resolved quickly with high dose steroids, recurred with steroid withdrawal, and abated with further steroid therapy. To our knowledge, this is the first reported case of fludarabine monophosphate associated pulmonary toxicity.
• Habib, M. P., & Engel, L. A. (1978). Influence of the panting technique on the plethysmographic measurement of thoracic gas volume.. The American review of respiratory disease, 117(2), 265-71. doi:10.1164/arrd.1978.117.2.265
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  In 7 normal subjects we studied the effect of different panting techniques on the measurement of thoracic gas volume (VTG). When inspiratory efforts against the occluded airway were performed primarily with intercostal and accessory muscles, the value of VTG was significantly larger than during efforts performed primarily with the diaphragm. The difference could be as large as 900 ml during the same occlusion and was due to compression and decompression of abdominal gas. The divergence of the measured VTG from the true VTG depended on the volume of abdominal gas (Vab) and the ratio of gastrict to mouth pressure changes (deltaPg/deltaPm). In our normal subjects, Vab was 358 +/- 65 ml (mean +/- SE) and deltaPg/deltaPm ranged from 0.7 to -2.5. In 10 randomly selected patients with a variety of pulmonary disorders, the mean value of deltaPg/deltaPm was 0.32. In one subject with asthma who increased his total lung capacity by one liter after exercising, deltaPg/deltaPm did not change significantly from the control value. Our results indicated that the pattern of panting is an important determinant of the accuracy of plethysmographic measurement of VTG. However, preliminary results from studies of patients suggest that the error is small and does not account for the large changes in lung volume measured in patients with acute asthma.