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Idiopathic pulmonary fibrosis in patients younger than 50 years.

OBJECTIVE: To assess clinical, radiological, histopathologic, and prognostic differences in younger patients with idiopathic pulmonary fibrosis (IPF). PATIENTS AND METHODS: This study consisted of patients younger than 50 years with IPF who were seen at the Mayo Clinic in Rochester, Minn, from January 1, 1994, to December 31, 2000. Clinical, radiological, and histopathologic data were abstracted from clinical records. Total lung capacity using plethysmography, vital capacity, diffusing capacity for carbon monoxide using the single-breath method, and alveolar volume using single-breath neon wash-in were measured. RESULTS: Our study population was composed of 16 men and 6 women with a median age of 45 years (range, 28-49 years). Median survival was 2.1 years, with 1- and 2-year survival rates of 68% and 53%, respectively. Of the 22 patients, 2 were current smokers, 14 were former smokers, and 6 had never smoked. Three patients had familial pulmonary fibrosis, 21 had bibasilar inspiratory crackles, and 10 had digital clubbing. Median total lung capacity was 56.2%, vital capacity was 51.0%, diffusing capacity was 45.5%, and alveolar volume was 65.0%. CONCLUSION: Although previous studies have suggested that younger age is a favorable prognostic factor in patients with IPF, we found that younger patients have the same poor prognosis as do older patients with this disorder. We observed no distinguishing differences in the clinical, radiological, and histopathologic features compared with those in older patients in whom the disorder is more common. Lung transplantation should be considered early in the treatment of younger patients with IPF.

Adult↗

Postoperative atelectasis: Intermittent positive pressure breathing, incentive spirometry, and face-mask positive end-expiratory pressure.

Postoperative atelectasis has been treated with inspiratory maneuvers in an attempt to increase functional residual capacity. We compared the effect of intermittent positive pressure breathing (IPPB), incentive spirometry, and 5-cm H2O positive end-expiratory pressure (PEEP) applied with a face mask on the transpulmonary pressure (PL) at the end of expiration of eight patients 24 to 34 hours after aortocoronary bypass graft insertion. Intermittent positive pressure breathing and PEEP increased expiratory PL during therapy. After IPPB, expiratory PL fell below control values and then returned toward, but did not reach, control values After PEEP was discontinued, expiratory PL returned to control values within the next 30 minutes. The results suggest that face-mask PEEP will increase functional residual capacity, that incentive spirometry has little or effect, and that IPPB may decrease lung volume after treatment.

Humans↗

Effect of low-dosage recombinant human growth hormone therapy on pulmonary function in hypopituitary patients with adult-onset growth hormone deficiency.

An impairment of the pulmonary function has been described in adult patients with childhood-onset growth hormone deficiency (GHD). We examined forced vital capacity (FVC), forced expiratory volume (FEV1), total lung capacity (TLC), functional residual capacity (FRC), residual volume (VR) and the index of inspiratory strength, middle tidal volume and tidal inspiratory time ratio (TV/I), in 29 patients with adult-onset GHD. Data were compared with those obtained in 46 healthy control subjects. Only the FEV1/FVC ratio was statistically different (p = 0.04) between the two groups of subjects. In a group of 15 GHD patients low dosages (0.5-1 IU/day s.c., bedtime) of recombinant human GH (rh-GH; n. = 8 subjects) or placebo (n. = 7) were given at random for a 6-month period. A significant increase in IGF-I levels was noted in the rh-GH-treated group (p = 0.04) but not in the placebo group. After the 6-month period no statistically significant changes in pulmonary function were found between the rh-GH-treated and placebo-treated GHD patients. This study shows that adult-onset GHD patients suffer from minimal impairment of pulmonary function. Low rh-GH dosages able to induce an increase in IGF-I levels do not improve pulmonary function. The effect of rh-GH on respiratory muscle strength could be related to the age at which GHD diagnosis is made, or induced only by high rh-GH dosages given for a long time.

Adult↗

Effect of continuous positive airway pressure on lung mechanics during high-frequency jet ventilation.

Six mongrel dogs were studied in a body plethysmograph to ascertain the effects of continuous positive airway pressure (CPAP) during high-frequency jet ventilation (HFJV), using an open system allowing gas entrainment. Increases in CPAP significantly reduced tidal volume. Increases in HFJV and inspiratory fraction caused progressively larger increases in functional residual capacity (FRC). Higher levels of CPAP dramatically reduced HFJV's effect on FRC, but lower levels of CPAP augmented this effect. At constant CPAP, tidal volume correlated well with the difference between peak airway pressure and CPAP, while the FRC change was correlated with the difference between end-expiratory pressure and CPAP. The relationship between end-expiratory airway pressure and total change in FRC was predictable from lung compliance at all levels of CPAP.

Animals↗

Prediction criteria for successful weaning from respiratory support: statistical and connectionist analyses.

OBJECTIVE: To develop predictive criteria for successful weaning of patients from mechanical assistance to ventilation, based on simple clinical tests using discriminant analyses and neural network systems. DESIGN: Retrospective development of predictive criteria and subsequent prospective testing of the same predictive criteria. SETTING: Medical ICU of a 300-bed teaching Veterans Administration Hospital. PATIENTS: Twenty-five ventilator-dependent elderly patients with acute respiratory failure. INTERVENTIONS: Routine measurements of negative inspiratory force, tidal volume, minute ventilation, respiratory rate, vital capacity, and maximum voluntary ventilation, followed by a weaning trial. Success or failure in 21 efforts was analyzed by a linear and quadratic discriminant model and neural network formulas to develop prediction criteria. The criteria developed were tested for predictive power prospectively in nine trials in six patients. RESULTS: The statistical and neural network analyses predicted the success or failure of weaning within 90% to 100% accuracy. CONCLUSION: Use of quadratic discriminant and neural network analyses could be useful in developing accurate predictive criteria for successful weaning based on simple bedside measurements.

Aged↗

Bronchial responsiveness to inhaled methacholine in young asymptomatic smokers.

Methacholine inhalation challenges were performed in 10 young smokers who denied having respiratory symptoms and in 10 nonsmokers of the same age. There were five males and five females in each group. The bronchoconstriction was evaluated with specific lung conductance (sGL), maximum partial (initiated from end-inspiratory lung volume) expiratory flows assessed at 40% vital capacity breathing air (Vmax40p air), and a He-O2 mixture (Vmax40p He), and with maximum complete flows breathing He-O2 [forced expiratory volume at 1 s (FEV1), Vmax50c He]. Dose-response curves were studied for 1) threshold concentration (TC) where values depart by more than two SD from base line; 2) provocative concentration (PC) causing a fixed fall in a parameter. Smokers differed significantly from nonsmokers for TC and PC accessed by Vmax40p He (P less than 0.001 and P less than 0.01, respectively), Vmax40p air (P less than 0.01), and Vmax50c He (P less than 0.01 and P less than 0.05, respectively). TC and PC estimated by sGL and FEV1 were not significantly different. Males and females showed a similar reaction.

Adult↗

Chest wall distortion and discharge of pulmonary slowly adapting receptors.

We assessed the effects of chest wall distortion, changes in lung volume, and abolition of airway smooth muscle tone on the discharge patterns of 92 pulmonary slowly adapting receptors (SAR) in decerebrate, spontaneously breathing cats. Distortion resulted from their inspiratory efforts against an occluded airway at functional residual capacity and at increased end-expiratory lung volumes. Approximately 40% of SAR increased discharge frequencies during occlusions. Modulation of SAR discharge during occlusions persisted after administration of atropine to eliminate airway smooth muscle tone. Phasic modulation of SAR discharge was eliminated during no-inflation tests after paralyzing the cats and ventilating them on a cycle-triggered pump. We conclude 1) parasympathetic modulation of airway smooth muscle tone makes no obvious contribution to SAR discharge in spontaneously breathing cats; 2) the no-inflation test (withholding of lung inflation during neural inspiration) in paralyzed and ventilated cats is a valid test for the presence of projections from SAR to medullary respiratory neurons; and 3) in the absence of tidal volume changes, distortion stimulates some SAR. Sensory feedback from receptors in the lung, not just those in the chest wall, may therefore provide information about abnormal chest wall configurations.

Abdomen↗

Bronchiolitis obliterans organizing pneumonia: definition and clinical features.

There are several bronchiolar diseases with different pathologic and clinical findings. Idiopathic BOOP is a distinct entity consisting of a flu-like illness, late inspiratory crackles, patchy infiltrates roentgenographically, and physiologically decreased vital capacity and diffusing capacity. Response to corticosteroid therapy is good and relapse does not occur if sufficient therapy is given. Bronchiolitis obliterans organizing pneumonia is an appropriate description of this entity. The term is specific because it includes bronchioles and alveoli and excludes disorders involving only alveoli such as organizing pneumonitis or organizing diffuse alveolar damage. The term is general enough to include a sufficient number of patients with a homogenous disorder. Furthermore, the entity can be described to clinicians and pathologists throughout the world in such a fashion that patient care and research can be standardized. Researchers from different centers studying the cause or utilizing treatment protocols are able to discuss a single BOOP entity rather than comparing results of a heterogeneous group of many different types of interstitial lung disorders. This will lead to breakthroughs in discovery of etiologic causes and new effective therapeutic regimens.

Bronchiolitis Obliterans↗

Pulmonary responses during cold induced acute pain.

Cold induced acute pain is associated with many autonomic responses of the cardiovascular system, skin conductance and pupil size. However, there are few reports suggesting changes in pulmonary function. Hence present study reports preliminary data on this. Acute pain was induced in 30 non-smoker males, 30-50 yrs of age by immersing hand in cold water and their respiratory rate (RR), tidal volume (TV), inspiratory and expiratory reserve volumes (IRV, ERV) and respective capacities, vital capacity (VC), force vital capacity (FVC), FEV1%, peak flow and flow rates at 75%, 50% and 25% of expired volume (V75,50,25) were measured. Acute pain parameters like pain threshold, tolerance and sensitivity were also recorded. Besides these, heart rate, blood pressure (systolic and diastolic), skin temperature of forehead and opposite palm were also measured. Comparisons were made between values recorded before, during and after cold induced pain. An increase in RR, RV, IC, EC, FVC, FVC%, FEV1 was observed during cold induced pain reflecting an acute state of sympathetic dominance. Positive correlations between heart rate and respiratory rate, and other respiratory with pain parameters were seen during period of induction of acute pain. Hence the study indicates that alterations in pulmonary profile form a part of multidimensional responses observed during cold induced acute pain.

Acute Disease↗

[Pulmonary function in infants with respiratory syncytial virus bronchiolitis].

OBJECTIVE: To observe the dynamics of pulmonary function in infants with respiratory syncytial virus (RSV) bronchiolitis. METHODS: The to test the pulmonary function of 31 infants with RSV bronchiolitis during acute phase at admission was tested. Pulmonary fuction test was performed for the second time among 17 out of the 31 infants during the clinical recovery phase, and performed for the third time among 10 out of the 17 infants one week after discharge. In the meantime pulmonary function test was performed in 74 healthy infants as controls. RESULTS: During the acute phase of RSV bronchiolitis, the respiratory rate (RR), peak tidal expiratory flow (PTEF), peak tidal flow/tidal volume (PF/Ve), respiratory system resistance (Rrs), and functional residual capacity per kilogram (FRC/kg) were significantly increased, while the inspiratory tidal volume (Vi), inspiratory volume per kilogram (Vi/kg), expiratory tidal volume (Ve), percent of tidal volume to peak tidal expiratory flow (%V-PF), terminal flows/peak expiratory flow (25/PF), respiratory system compliance (Crs), and respiratory system compliance per kilogram (Crs/kg) were significantly decreased as compared with those in healthy infants. Ratio of mid-expiratory to mid-inspiratory flow (ME/MI) and respiratory system time constant (Trs) showed no statistically significant differences. The tidal breathing flow-volume (TBFV) loop displayed a concave expiratory curve. During the clinical recovery phase, the above abnormal indexes showed significant improvement, except for the %V-PF, 25/PF and Crs/kg which were still lower as compared with those in healthy infants, most indexes had returned to normal. The TBFV loop showed mild decelerating expiratory limb. One week after discharge all of the indexes returned to normal. CONCLUSION: In the acute phase of RSV bronchiolitis higher resistance in small airway and obstructive ventilatory disturbance can be seen. Some of the indexes remain abnormal during the clinical recovery phase. However, the abnormalities disappear in a short time. Pulmonary function test is a valuable way for surveillance of the course and prognosis of RSV bronchiolitis. %V-PF, 25/PF, and FRC/kg are sensitive indexes.

Bronchiolitis, Viral↗

Spirometric diagnosis of upper airway obstruction.

We evaluated the results of routine spirometry in patients with well-documented upper airway obstruction (UAO) to determine if this readily available form of pulmonary function testing could reliably identify patients with this abnormality. Our results indicate that, although individual standard spirometric indexes could not identify these patients, ratios derived from these indexes provided excellent discrimination between patients with UAO and patients with a variety of lung diseases. A ratio of maximal voluntary ventilation to forced expiratory volume in 1 s of less than 25 was present in ten (66%) of 15 patients with UAO and only one (1%) of 100 comparison patients. A ratio of forced inspiratory flow between 25% and 75% of the vital capacity to forced expiratory flow between 25% and 75% of the vital capacity of less than 1 was found in 12 (80%) of 15 patients with UAO, but in only four (4%) of 100 comparison patients. All patients with UAO had one ratio abnormal. We conclude that spirometry remains a valuable procedure in the diagnosis of UAO.

Adult↗

Pulmonary function following 'pretreatment' dose of pancuronium in volunteers.

The effect of a pretreatment dose (0.014 mg/kg) of pancuronium bromide on pulmonary function tests in 15 healthy volunteers was investigated. Ventilatory flow volume loops and maximum voluntary ventilation were determined before and 1 and 3 minutes following administration of the pancuronium. Calculation of the pulmonary function from the flow volume loops revealed statistically significant decreases in forced expiratory flow at 50% of expired volume, forced expiratory volume at 1 second and 3 seconds, peak inspiratory flow, peak inspiratory flow at 50% of inspired volume, forced vital capacity, and maximum voluntary ventilation. Significant pulmonary dysfunction associated with dyspnea was seen in four subjects and one subject had to be artificially ventilated and pancuronium had to be reversed with prostigmine. Ventilation should be closely monitored in patients following pretreatment doses of pancuronium in view of frequent atypical responses.

Adult↗

Nitrogen single breath test, flow-volume curves and spirometry in healthy children, 7-18 years of age.

One hundred and forty school children, 75 boys and 65 girls, aged 7-18 years, underwent the following lung function tests: closing volume, slope of the alveolar plateau, maximal expiratory and inspiratory flows at 75, 50 and 25% of vital capacity, static and dynamic lung volumes. Lung volumes and maximal flows increase with height in an exponential way, the exponents varying between 2.6 and 3.1, while closing volume in per cent of vital capacity and the slope of the alveolar plateau decrease linearily with increasing height. Regression equations are given for each sex with height as determinant.

Adolescent↗

Vital capacities in acute and chronic airway obstruction: dependence on flow and volume histories.

The aim of this study was to investigate whether measurements of vital capacity (VC) are affected by the direction of the manoeuvre (inspiratory vs expiratory) and by the rate of expiratory flow. The study was performed on 25 individuals with chronic airway obstruction (CAO) and a forced expiratory volume in one second (FEV1) (expressed in standardized residuals (SR)) of -2.0+/-1.4 SD (CAO group), and 10 asthmatic subjects with methacholine (MCh)-induced bronchoconstriction (FEV1 -23+/-1.02 SR) (MCh group). VCs were measured during fast inspiration following both slow (FIVCse) and forced (FIVCfe) expiration from end-tidal inspiration to residual volume (RV), and during slow (EVC) or forced (FVC) expiration from total lung capacity (TLC). In the CAO group, FVC was the smallest volume (3.75+/-1.03 L) and significantly different from the other three estimates of VC; FIVCse (4.03+/-0.91 L) was the largest volume and significantly different from FVC and FIVCfe (3.83+/-0.98 L). In the MCh group, FVC (4.16+/-0.94 L) and EVC (4.19+/-0.89 L) were the largest volumes, although only the difference between FVC and FIVCfe (3.76+/-0.81 L) reached statistical significance. These data suggest that both flow and volume histories contribute to decreased vital capacities during bronchoconstriction. However, whereas increasing expiratory flow always tends to decrease vital capacity, the volume history of full inflation has different effects in chronic and acute bronchoconstriction, probably due to different effects on airway calibre. These results stress the importance of using standardized manoeuvres in order to obtain comparable values of vital capacity.

Acute Disease↗

Respiratory mechanics and gas exchange during one-lung ventilation for thoracic surgery: the effects of end-inspiratory pause in stable COPD patients.

OBJECTIVE: To examine the effects of end-inspiratory pause (EIP) of different durations on pulmonary mechanics and gas exchange during one-lung ventilation (OLV) for thoracic surgery. DESIGN: A prospective clinical study. SETTING: A university hospital. PARTICIPANTS: Eleven patients undergoing elective pulmonary resection with pulmonary hyperinflation on their preoperative pulmonary function studies. INTERVENTIONS: Patients were anesthetized, paralyzed, and intubated with a double-lumen endotracheal tube. Their lungs were ventilated with a Siemens 900C ventilator (Siemens; Solna, Sweden), with constant inspiratory flow. Tidal volume, respiratory rate, and inspiratory time were kept constant during the study. MEASUREMENTS AND RESULTS: During one-lung ventilation in the lateral decubitus position, three levels of EIP (0%, 10%, and 30%) were applied to the dependent lung in random order. After 15 minutes on the given ventilatory pattern, end-inspiratory and end-expiratory occlusions of at least 5 seconds were performed to obtain respiratory mechanics data. Arterial blood gas samples were drawn to assess gas exchange. Altering the duration of end-inspiratory pause from 0% to 30% resulted in a significant increase in intrinsic positive end-expiratory pressure (PEEPi) from 4.1 cm H2O to 7.0 cm H2O. Arterial oxygenation was significantly decreased from 109.7 to 80.5 mmHg and there was a significant negative correlation between the value of partial pressure of arterial oxygen (PaO2) and PEEPi by altering the duration of end-inspiratory pause. From the preoperative pulmonary function studies, the value of functional residual capacity (FRC) (% predicted) showed a significant negative correlation with the PaO2 changes. Partial pressure of arterial carbon dioxide (PaCO2) was not altered significantly by increasing the duration of end-inspiratory pause. CONCLUSION: During the period of OLV in the lateral position of patients with preexisting pulmonary hyperinflation, the magnitude of PEEPi increased and oxygenation decreased significantly, whereas the efficacy of ventilation was not changed by the addition of an end-inspiratory pause to the ventilatory pattern. Because arterial oxygenation is affected by the presence of pulmonary hyperinflation, the method of ventilation should take into account the magnitude of preoperative pulmonary hyperinflation.

Aged↗

Central and peripheral components of diaphragmatic fatigue during inspiratory resistive load in cats.

The development of fatigue was investigated in the diaphragm of anaesthetized, tracheostomized, spontaneously breathing cats during restricted air flow. Ventilation, transdiaphragmatic pressure (Pdi), integrated electrical activity of diaphragm (Edi) and phrenic nerve (Eph) were measured simultaneously and expressed as a percentage of values at unloaded breathing. Inspiratory loads were 60, 70 and 80% of Pdi max. The Pdi max was measured by airway occlusion at functional residual capacity. The duration of loads was 40-60 min. The diaphragmatic fatigue developed only during heavy inspiratory loading (80% Pdi max). During the first 10 min of heavy load Pdi, Edi and Eph increased to 905 +/- 60%, 248 +/- 20% and 229 +/- 24%, respectively (P < 0.01), and then began to fall gradually. Ventilation declined to 39 +/- 3% after 60 min of heavy load (P < 0.01), resulting in acute hypercapnia and hypoxia. Initial fatigue appeared as a decrease in Pdi (to 781 +/- 63%) and parallel decline in Edi (to 233 +/- 21%) after 30 min of load (P < 0.05). Phrenic nerve activity did not change during this stage. These data suggest a peripheral basis of diaphragmatic fatigue, related to disorders in neuromuscular transmission. After 60 min of heavy load, Pdi fell to 675 +/- 49%, Edi declined to 209 +/- 28% and Eph decreased to 189 +/- 25%. We interpret the decrease in phrenic nerve activity as a weakening of central inspiratory drive and development of the central component of diaphragmatic fatigue in the last stage.

Animals↗

An alternate method for the determination of functional residual capacity in a plethysmograph.

The validity of measuring thoracic gas volume using a single inspiratory effort against an occlusion (Vtginsp) was determined in children and young adults (8 normal control subjects and 17 patients with cystic fibrosis [CF] or asthma). In addition, the validity of the measurement of Vtg at FRC in children at a low panting frequency (Vtgpant) was also determined. During both the panting (encouraged to be about 1 Hz) and inspiratory maneuvers, mouth pressure (Pm) and esophageal pressure (Pes) were measured simultaneously. Hence, Vtgpant and Vtginsp were determined using both delta Pm and delta Pes. Vtginsp using delta Pm was found to be similar to Vtginsp using delta Pes. Values for Vtgpant using either delta Pm or delta Pes were also found to be similar. The percent difference between Vtginsp (using delta Pm) and the average of Vtgpant and Vtginsp (using delta Pes for both) was calculated as an indication of the error of the inspiratory method. The error ranged from -13 to +13% and did not correlate with indices of air-flow limitation or hyperinflation. We have found that Vtginsp can be used to determine FRC in normal children and young adults as well as in those with CF or asthma. In addition, we have also validated the use of Vtgpant at a low panting frequency in these subjects.

Adolescent↗

Spirometric gated quantitative computed tomography of the lung in healthy smokers and nonsmokers.

RATIONALE AND OBJECTIVES: The authors investigated the influence of cigarette smoking on healthy, asymptomatic smokers and nonsmokers with the help of spirometric triggered quantitative computed tomography. In our prospective study, the authors compared conventional lung function parameters with the computed tomography values (lung attenuation, lung area). METHODS: The study group comprised 40 healthy volunteers consisting of 20 smokers and nonsmokers (20 females and 20 males). The corresponding groups have been matched concerning their age, height, body mass, (cigarette) pack years. Computer tomography scans were triggered at 35%, 50%, 70% and 95% of vital capacity at a defined apical and a basal level. RESULTS: Functional residual capacity (FRC), total lung capacity and airway resistance showed close correlations to lung parenchymal attenuation values especially at full inspiration and expiration. For example, the authors found a correlation coefficient of r = -0.845 (P < or = 0.001) concerning the FRC and lung attenuation values in the apical lung at 35% of vital capacity in male smokers. Male smokers proved to have a significantly higher pulmonary lung density at all inspiratory states than the other groups (P < or = 0.05; Student's t test). Although male smokers had a higher vital capacity they showed a smaller cross-sectional area increase of the lung during inspiration than nonsmokers. This phenomenon is a result of the decreasing compliance of the smoker's lung, due to small airways disease and hypoxic vasoconstriction. CONCLUSIONS: Spirometric-triggered quantitative computed tomography has proved to be a sensitive diagnostic device for the investigation of early pathomorphologic changes in healthy, asymptomatic cigarette smokers.

Female↗