Bronchoscopic lung volume reduction with endobronchial valves for patients with heterogeneous emphysema and intact interlobar fissures (the BeLieVeR-HIFi trial): study design and rationale.

Although lung volume reduction surgery improves survival in selected patients with emphysema, there has been ongoing interest in developing and evaluating bronchoscopic approaches to try to reduce lung volumes with less morbidity and mortality. The placement of endobronchial valves is one such technique, and although some patients have had a significant improvement, responses have been inconsistent because collateral ventilation prevents lobar atelectasis. We describe the protocol of a trial (ISRCTN04761234) aimed to show that a responder phenotype, patients with heterogeneous emphysema and intact interlobar fissures on CT scanning, can be identified prospectively, leading to a consistent benefit in clinical practice.

Capsaicin cough sensitivity in bronchiectasis.

BACKGROUND: Bronchiectasis is a suppurative airway disease characterised by persistent cough and sputum production associated with bronchial dilatation. A study was undertaken to determine whether cough sensitivity is increased in bronchiectatic patients. METHODS: Twenty two patients with bronchiectasis and 20 healthy non-smoking controls matched for age and sex were recruited into the study. Quality of life (Leicester Cough Questionnaire score), total cough symptom score, and extent of bronchiectasis on HRCT scans were recorded. Cough sensitivity was assessed using incremental inhalation of capsaicin concentrations; the concentration at which 5 or more coughs occurred (C5) was recorded. RESULTS: Patients with bronchiectasis had increased sensitivity to capsaicin compared with controls (mean (SE) log10 C5 1.22 (0.20) v 1.89 (0.21); p<0.03). Capsaicin sensitivity correlated positively with the Leicester Cough Questionnaire score (r = 0.64; p = 0.005) and inversely with the total cough symptom score (r = -0.58; p = 0.004), but not with the extent of the disease. It also correlated with forced expiratory volume in 1 second (FEV1) in litres (r = 0.58; p = 0.005) but not with FEV1 % predicted. Capsaicin sensitivity was not related to the presence of infected sputum or to corticosteroid or bronchodilator use. CONCLUSIONS: : Patients with bronchiectasis have a sensitive cough reflex which reflects the severity of cough symptoms. A measure of cough severity could be part of health assessment for patients with bronchiectasis.

Peripheral airways obstruction on high-resolution computed tomography in chronic severe asthma.

Long-standing chronic severe asthma may be associated with structural changes of both proximal and distal airways. To assess these changes, high-resolution computed tomography (CT) using an Imatron Ultrafast CT scanner with 3 mm thick sections at 10 min intervals was performed at full inspiration. A limited set of CT sections was also obtained on full expiration. Twenty-four chronic severe asthmatic patients (age, 47.0 +/- 2.4 years; FEV1, 56.5% +/- 4.1% of predicted) were studied. The scans were assessed independently by two radiologists. While concomitant dilatation and thickening of intrapulmonary airways were observed in 12 patients, air trapping as assessed by areas of increased lucency on expiratory scans was noted in 20. The mean expiratory-to-inspiratory cross-sectional area (Exp/Ins) was 75.9% +/- 2.0%, compared with 44.6% +/- 1.0% in historical non-asthmatic subjects. FEV1 (% predicted) correlated with Exp/Ins and with CT features of air trapping (both rs = 0.60; P < 0.001) but not with airway dilatation or thickening. Our data indicate the presence of peripheral airways obstruction in chronic severe asthma, which may be one of the underlying reasons for increased severity of asthma.

Non-breath-hold lung magnetic resonance imaging with real-time navigation.

Magnetic resonance imaging (MRI) with navigating techniques based on consecutive breath-holds demand a level of respiratory control that is often beyond the capability of patients with lung disease. The objectives of this investigation were to develop and evaluate a navigating technique for lung MRI that does not rely on patient cooperation. Navigating techniques were implemented at 0.5 T using conventional imaging techniques of short echo-time and imaging during normal breathing in the diastolic phase of the cardiac cycle. A column of spins, orthogonal to the diaphragm, was excited both immediately before and after the imaging segment. These signals were processed in real time to provide the position of the lung-diaphragm interface. An imaging segment was considered correctly acquired only when the interface position was within the acceptance window both before and after the acquisition of the segment. A distribution of lung-diaphragm interface positions obtained during normal respiration was employed to define the acceptance window. In the case of multislice techniques, the position of the lung-diaphragm interface immediately before the imaging segment was also employed to decide which phase-encoding step to acquire next, therefore reducing the apparent frequency of the respiratory motion. A distribution of interface positions, updated in real time, served as a reference for the allocation of phase-encoding steps according to diaphragm position. The lung images obtained represent a significant advance in image quality, improving further the ability of MR to detect and monitor pulmonary disease. Motion artifacts were reduced, and images reliably demonstrated smaller vessels, which are not normally visible without navigation.

Accuracy of CT in predicting the cause of bronchiectasis.

There are many reports that state that the distribution and pattern of bronchiectasis may be sufficiently characteristic for a specific cause to be suggested. The aim of this study was to determine whether experienced chest radiologists could confidently and accurately diagnose various aetiologies of bronchiectasis from the computed tomography (CT) pattern of disease alone. CT scans of 108 patients with bronchiectasis of various causes (67 with idiopathic bronchiectasis, 10 with allergic bronchopulmonary aspergillosis, 12 with syndromes of impaired mucociliary clearance, 12 with hypogammaglobulinaemia and seven with adult cystic fibrosis) were assessed by three chest radiologists without knowledge of clinical data. Each observer listed the three most likely diagnoses in order of probability. In addition, a level of confidence on a 3-point scale was assigned to the first choice diagnosis. A correct first-choice diagnosis was made in 45% of readings. A high confidence level was given in only 9% of the first choice readings. Of these, a correct diagnosis was reached in 35%. There was poor interobserver agreement (mean kappa = 0.20). In conclusion, we found that the causes of bronchiectasis cannot be reliably diagnosed on the basis of CT appearances alone.

CT findings in bronchiectasis: limited value in distinguishing between idiopathic and specific types.

OBJECTIVE: The purpose of this study was to determine whether the pattern and distribution of bronchiectasis shown on CT scans can be used to discriminate between idiopathic cases and those with an identifiable cause. MATERIALS AND METHODS: The CT scans of 168 patients with chronic purulent sputum production and who were suspected of having bronchiectasis were analyzed (117 patients with idiopathic bronchiectasis, 15 with allergic bronchopulmonary aspergillosis, 15 with hypogammaglobulinemia, 15 with impaired mucociliary clearance, and seven with cystic fibrosis diagnosed in adult life). The scans were analyzed in random order by two observers. The extent, site, type, and lobar distribution of bronchiectasis and the severity of bronchial dilatation and bronchial wall thickening were scored. The frequency of these features in the known-cause groups was compared with that in the idiopathic group to identify any significant differences. RESULTS: Compared with idiopathic bronchiectasis, no significant lobar predominance was seen in any of the known-cause groups, apart from a higher frequency of lower lobe involvement in the patients with syndromes of impaired mucociliary clearance (p < .02). The bronchiectasis of allergic bronchopulmonary aspergillosis and adult cystic fibrosis was more often widespread (five or six lobes involved (p < .001 and p < .01, respectively) than idiopathic bronchiectasis. Central bronchiectasis was more common in allergic bronchopulmonary aspergillosis (p < .005), although the sensitivity when this was used as a diagnostic feature was only 37%. In all groups, cylindrical bronchiectasis was the most common type, with varicose and cystic bronchiectasis occurring more frequently in allergic bronchopulmonary aspergillosis (p < .01). On multiple regression analysis, allergic bronchopulmonary aspergillosis and adult cystic fibrosis showed more extensive disease than idiopathic bronchiectasis (p < .0005 and p < .001, respectively), independent of other CT features. In hypogammaglobulinemia, dilatation of the bronchial lumen was less than in idiopathic bronchiectasis (p < .02) independent of disease extent and bronchial wall thickness. CONCLUSION: Although differences in distribution and morphology of bronchiectasis may be seen on CT scans in groups of patients with bronchiectasis of different causes, CT findings applied to individual patients are of limited value in discriminating between idiopathic bronchiectasis and bronchiectasis of various known causes.

Magnetic resonance scanning in cystic fibrosis: comparison with computed tomography.

Comparison has been made between two different spin-echo sequence MR scans and CT scans of the lungs in 17 patients with cystic fibrosis. Scans were assessed for bronchial dilation, bronchial wall thickening and mucus plugging. The resolution of MR does not, at present, compare with CT. TE7 ms matched with CT for demonstrating the extent of bronchiectasis whereas TE30 ms scans were inferior to CT. Stronger background lung signal and less artefact was seen on TE7 ms scans compared with TE30 ms scans. MR is a developing technology that does not involve ionizing radiation which, with further refinement, may prove to be useful in imaging lung pathology in cystic fibrosis.

Low tissue gastrin content in the ovine distal duodenum is associated with increased percentage of G34.

1. In adult sheep and in lambs, over 95% of gastrin in the abomasal antrum was G17 with small amounts of G34 and lesser amounts of Component I. 2. Low gastrin concentration in the proximal duodenum was associated with a reduced percentage of G17. 3. The proportion of G34 increased progressively down the duodenum from a mean of 7% proximally to 47% in the most distal segment, and correlated negatively in any segment with the gastrin content. 4. In both the antrum and proximal duodenum, 60-70% of the G17 was in the sulphated form. 5. The gastroepiploic venous serum contained less G17 and more G34 than the tissues and up to 19% G14.

Role of right heart receptors in the control of renin, vasopressin, and cortisol secretion in dogs.

We have reported that increased left heart pressure inhibits increases in plasma renin activity (PRA), arginine vasopressin (AVP), and cortisol during arterial hypotension. The goal of this study was to determine whether increases in right heart pressure also inhibited hormonal responses to hypotension. Seven dogs were chronically instrumented with inflatable cuffs around the ascending aorta (AA), the pulmonary artery (PA), and the thoracic inferior vena cava (IVC), as well as with catheters in both atria, the abdominal aorta, and vena cava. The IVC, the PA, and the AA cuffs were inflated on different days to cause step reductions in mean arterial pressure (MAP) of 5, 10, 20, and 30% below control MAP. Graded constriction of the AA caused large increases in left atrial pressure and plasma atrial natriuretic peptide (ANP), but had no effect on plasma AVP or cortisol and caused only a small increase in PRA at the maximal reduction of MAP. Constriction of the IVC reduced both atrial pressures and plasma ANP, but stimulated increases in PRA, AVP, and cortisol. Constriction of the PA increased right atrial pressure and plasma ANP and caused increases in plasma AVP and cortisol that were similar to responses during IVC constriction, but the PRA response was only half (P < 0.05). These results indicate that increasing pressure on the right side of the heart can attenuate the PRA response to hypotension, and suggest that the inhibition is mediated by the rise in plasma ANP.

Advanced multiple beam equalization radiography (AMBER) in the detection of diffuse lung disease.

To evaluate the effects of scanning equalization radiography (SER) on the detection of diffuse lung disease a clinical comparison between an Advanced Multiple Beam Equalization Radiography (AMBER) unit and conventional chest radiography was performed. Even though the overall detection of focal pulmonary lesions with the AMBER unit has been shown to be significantly higher than with conventional radiography because of the improved demonstration of the costophrenic and retrocardiac regions, the utility of AMBER in the demonstration of diffuse lung disease has not been established. Twenty-one patients with diffuse lung disease (fibrosing alveolitis or sarcoidosis) and six patients with no pulmonary disease had high kVp frontal and lateral chest radiographs on both an AMBER unit and a conventional chest stand. The pooled results of five observers using Receiver Operating Characteristic (ROC) analysis indicate that there is a slight improvement but no statistically significant difference in observer performance between AMBER (Area under the ROC curve AZ = 0.934) and conventional radiography (AZ = 0.868) in the task of detecting diffuse lung disease.

Some physiological and pharmacological factors affecting uterine motility as measured by electromyography in the mare.

Two intact and 2 ovariectomized mares aged 3-16 years had bipolar electrodes implanted in the myometrium to measure electromyographic (emg) activity during normal and exogenously simulated (with oestrogen and progesterone) cyclical activity (anoestrus, transition, oestrus and dioestrus). Oxytocin, cloprostenol, propantheline bromide and clenbuterol were administered during each cycle stage. In 1 mare, emg activity was recorded during natural breeding (4 times) and through the first 20 days of pregnancy. Simultaneous intrauterine pressure recordings (IUP) using an open tipped catheter system were taken occasionally. For mares in oestrus, we recorded short bursts of high amplitude emg activity separated by quiet periods, a pattern that is indicative of uterine contractions. During dioestrus the duration of emg activity increased, but amplitude decreased and interspersed quiet periods were less well defined, indicative of uterine tonus. The emg patterns seen in anoestrus and transition were intermediate. At breeding there was a short-lived increase in emg activity, unlikely to be caused by endogenous hormone release. During early pregnancy the emg characteristics varied depending on whether the fertilized ovum was in the oviduct, migratory or fixed, with emg activity increasing to 100% after Day 16 when uterine tone is maximal. Oxytocin and cloprostenol caused prolonged emg activity followed initially by a short burst pattern that was most pronounced in oestrus and least in dioestrus and suggests uterine motility is stimulated to a greater extent during oestrus. Propantheline decreased emg activity, whereas cloprostenol caused minimal changes. IUP increased with uterine stimulants and decreased with uterine relaxants, but showed little variation between cyclic states. There was little correlation, statistically or visually, between IUP and emg activity during the oestrous cycle with or without drug treatment. Because emg analysis gave consistent results and demonstrated significant differences between oestrus and dioestrus that neither agreed nor correlated with IUP, the validity of the IUP recording technique used in this study (as well as those used in general for the mare) is questioned. It is suggested that extrauterine factors such as intestinal motility and intra-abdominal pressure changes could influence IUP responses.

Airway hypersensitivity induced by Ascaris suum extract in New Zealand Romney sheep.

Sheep from local farms with and without previous exposure to pigs were tested for their skin and airway responses to a commercial Ascaris suum antigen. There was an immediate reaction to intradermal injection of the antigen in 90% of 101 sheep. A bronchial provocation test by aerosol of the same antigen was undertaken on 43 of the sheep with a positive skin reaction. About 70% of sheep showed an immediate airway response to the antigen as an aerosol, reflected as a significant increase in airway resistance and/or decrease of dynamic lung compliance. The mean peak airway resistance and mean lowest dynamic lung compliance were 165% above and 61% below their baselines, respectively. No significant changes were recorded when the same animals were given an aerosol of phosphate buffered saline. Similarly, no correlation was found between the degree of skin reaction and the magnitude of bronchoconstriction (p>0.05). The sheep with previous exposure to pigs showed no significant differences in airway responses to antigen challenge, although they showed significantly greater skin reactions than those without exposure to pigs. These results indicate that the majority of Romney sheep in the Manawatu have a natural skin and airway sensitivity to A. suum antigen and may therefore be used as an animal model to study human airway hypersensitivity. The origin of this sensitivity has yet to be determined.

Abnormal regional distribution of ventilation in middle-aged smokers: comparison of changes in 81Krm ventilation scans and computed tomography of the lung.

In 1980 we found that abnormalities in regional distribution of ventilation, as assessed by 81Krm lung scans, were common in middle-aged smokers with normal chest radiographs and mild impairment of overall lung function. In 1984 we repeated 81Krm scans in 16 continuing smokers then aged 50-64 years and with mean forced expiratory volume in one second 93% (20 SD) of predicted values who had previous 81Krm scans performed in 1980. To assess the role of disease of the peripheral airspaces in causing abnormal regional ventilation, we also obtained computed tomograms (CT) of the lungs and measured carbon monoxide transfer of the lungs in these men. Krypton scans in seven men who had normal or minor focal defects of ventilation in 1980 were unchanged in 1984. Scans in seven of the nine men who had abnormal scans in 1980 remained abnormal in 1984 but there was no overall deterioration in the abnormality of ventilation in these men; in men with similar grading in 1980 and 1984 some of the peripheral defects present in 1980 had resolved and some new abnormal areas had appeared. Minor localised abnormalities of CT scans, as assessed visually, were present in eight of the 16 men and were associated with lower values of carbon monoxide transfer coefficient (mean 78% vs 98% predicted in men with normal scans, P less than 0.01) and lung density (mean -894 vs -869 HU in men with normal scans, P less than 0.054) suggesting the CT changes were due to alveolar destruction. Abnormality of the krypton scan was not significantly associated with abnormality of the CT scan or with a reduction in carbon monoxide transfer. The results of the krypton lung scans confirm that non-uniformity of regional ventilation is often present in asymptomatic middle-aged smokers and suggest that this non-uniformity is in part due to temporary occlusion of airways. Abnormality in regional ventilation was not associated with the anatomical changes shown by the CT scan, suggesting that airway narrowing was more important than alveolar destruction in causing regional abnormalities of ventilation in these men.

Computed tomography of folded lung.

Computed tomography (CT) scans of 22 examples of folded lung in nine patients were reviewed. The most important CT criteria of folded lung are the presence of vessels and bronchi running in a smooth curvilinear fashion towards a peripheral mass with an ill defined central edge associated with pleural thickening. These features were seen in all 22 examples. The lesions are frequently multiple (eight out of nine patients). When these features are present the diagnosis can be made without recourse to biopsy or thoracotomy. Enhancement with intravenous contrast medium is unnecessary and does not provide any extra useful information. Various other previously described criteria such as air bronchograms are not necessary for the diagnosis.

Computed tomography appearances of pulmonary alveolar proteinosis.

The computed tomography appearances of six patients with pulmonary alveolar proteinosis are reported. In all patients the appearances are similar and are unlike pulmonary opacities in any other disease; in one patient they suggested the diagnosis. The CT appearances correlate well with histology and demonstrate septal thickening within lung involved by the disease.

Ultrasound, CT, and MRI comparison in primary and secondary tumors of the liver.

Thirty-five patients with surgically removed or percutaneous biopsy-proven tumors were examined by ultrasound, computed tomography (CT), and magnetic resonance imaging (MRI). This retrospective study describes the appearance of the primary tumors and metastases and compares the sensitivity and specificity of the 3 imaging methods. Ultrasound, CT, and MRI examinations as well as clinical, operative, and/or histologic data were available for all 35 patients. Paramagnetic contrast agent gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) was used in 23 patients and a short TI inversion recovery MRI sequence was used in 23 patients, in addition to various spin echo MRI sequences. Thirteen patients were examined using both Gd-DTPA and the short TI inversion recovery sequence. Our comparative study--based on the following criteria: detection, size, location of the tumor, and portal vein involvement and bile duct dilatation--demonstrated an advantage of MRI over ultrasound in 16 of 35 cases, equal results in 17 of 35 cases and a disadvantage of MRI compared to ultrasound in 2 of 35 cases. With the identical criteria, MRI proved to be more informative than CT in 10 of 35 cases, equal in 21 of 35 cases, and less informative in 4 of 35 cases.

Long term follow-up of patients with Cushing's disease treated by interstitial irradiation.

The first 86 patients with Cushing's disease treated with interstitial irradiation (by needle implantation) as the sole therapy were reviewed. In the 82 patients who were reassessed 1 yr after treatment 63 (77%) achieved remission. This study comprises the outcome and complications in the 54 patients who had a remission and whom we were able to follow. The follow-up period ranged from 3-26 yr (mean, 10.5) from the time of remission. No instance of clinical or radiological relapse has occurred. Of these 54 patients, yttrium-90 alone was used in 32, of whom 12 (37%) required corticosteroid or T4 replacement therapy in a mean time of 3.5 months; in 7 of these 12 we elected to give an ablative dose. Gold-198 alone was used in 15 patients, of whom 7 (47%) developed hypopituitarism in a mean time of 76 months. Both isotopes were used in 7 patients. A diurnal serum cortisol rhythm was found in 28 of the 31 patients who were not receiving corticosteroid therapy. In 5 of the 7 patients with an initially abnormal pituitary fossa, serial radiological studies revealed remodelling in 3. There have been no complications in the last 17 years. Pituitary implantation with yttrium-90 is an effective alternative to transsphenoidal hypophysectomy, with a high remission rate, no recurrence (as yet), no operative complications, and avoidance of hormone replacement in the majority.

Neurophysiologic maps of cutaneous innervation of the external genitalia of the ram.

The area of skin innervated by the afferent fibers in a peripheral nerve is called the cutaneous area (CA) of that nerve. Mapping of those areas that were responsive to movement of wool/hairs in the genital region of 18 anesthetized rams, combined with subsequent identification of spinal nerves and dissection of the pudendal nerve plexus, indicated considerable differences in the extent of the CA and the origins of cutaneous branches from the pudendal plexus. The CA of the proximal and distal cutaneous branches of the pudendal nerve (or plexus) overlapped craniocaudally by approximately one-half, and the latter included most of the skin of the ipsilateral half of the scrotum. The CA of the deep perineal and caudal rectal nerves lay immediately adjacent to the anus. The CA of the scrotal branches of the pudendal nerve were restricted primarily to the scrotum. Fascicles in the dorsal nerve of the penis irregularly supplied CA along the length of the prepuce and consistently supplied the cranial free end of the prepuce. The CA of the ventral cutaneous branches of the caudal thoracic spinal nerves, the first 2 or 3 lumbar spinal nerves, and the genitofemoral nerve extended to the midline of the prepuce. Overlapping of CA was extensive, especially on the prepuce.

The afferent innervation of the face of sheep and goats.

The sensory innervation of the maxillary hairy skin and buccal mucous membrane was studied in anaesthetised sheep and goats. An electrophysiological technique isolated 47 single afferent units from the infraorbital nerve under chloralose or halothane anaesthesia. Mechanoreceptors of hairy skin were located in association with the following features: sinus hairs (n = 9); central primary hairs (n = 18); clear marginal hairs (n = 7) and skin-not-hair (n = 3). Units responded to hair tip displacement of 35 to 50 microm. Afferent units were also located in the mucous membrane of the cheek either associated with conical papillae (n = 8), or unassociated with papillae (n = 1). Receptor responses associated with hairs were classified as rapidly adapting (n = 18) and slowly adapting (n = 18) mechanoreceptor responses during sustained hair deflection. Seven mechanoreceptors of hairy skin and mucous membrane were excited by a fall in surface temperature. Two specific cold thermoreceptors were found: one in hairy skin and one in the mucous membrane. These units had phasic discharges during abrupt thermal depression and static discharges at constant surface temperatures. All afferent units had myelinated axons as indicated by their conduction velocities (range 20 to 57 m sec-1, mean 34 m sec-1). It is concluded that the mechanoreceptors identified had similarities with those of other mammalian species and some distinct differences. An interesting feature of mechanoreceptors in the buccal mucosa was their cold sensitivity. They therefore shared characteristics with mechanoreceptors in the penile mucosa of the ram and tongue of the sheep.