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PubMed1993

Proliferating alveolar macrophages in BAL and lung function changes in interstitial lung disease.

In interstitial lung disease, the number of alveolar macrophages (AMs) can be increased. This may be caused by recruitment of precursor cells from peripheral blood and/or local proliferation in the lung. We therefore analysed proliferation, by studying both the expression of the nuclear proliferation antigen, Ki67, and the deoxyribonucleic acid (DNA) content, using the Feulgen reaction followed by cytometry. The patients had interstitial lung disease, i.e. sarcoidosis (n = 20), extrinsic allergic alveolitis (n = 20), idiopathic lung fibrosis or lung involvement in collagen-vascular disease (n = 19). In all patient groups there was a significant increase in proliferating AMs compared to healthy controls (4.2 versus 1.4% Feulgen, 2.1 versus 0.5% Ki67), with a significant correlation between these two parameters. A positive correlation was also found in bronchoalveolar lavage (BAL) between numbers of lymphocytes and proliferating cells in sarcoidosis and in fibrosis. In fibrosis, numbers of eosinophils and proliferating cells were also positively correlated. Our main finding was, however, a positive correlation between numbers of proliferating cells (Feulgen) and lung function parameters, especially vital capacity and oxygen tension (PO2) at rest, in patients with sarcoidosis and lung fibrosis. By contrast, in extrinsic allergic alveolitis, no correlation could be observed between proliferating cells and cell population or lung function. Our results suggest that local proliferation of macrophages is an important element in interstitial lung disease.

Adult↗
PubMed1990

Resting energy expenditure in interstitial lung disease.

Because interstitial lung disease increases the work of breathing, the aim of this study was to determine if this condition is associated with increased energy requirements. A group of 12 clinically stable patients with interstitial lung disease was studied. Patients with a history of weight loss had significantly more severe lung volume restriction. Regression analysis showed that 42% of body weight variation was explained by vital capacity (p less than 0.025). Resting energy expenditure was measured by standard methods of indirect calorimetry. The measurements were performed with a ventilated hood during prolonged steady-state periods after an overnight fast. We found that resting energy expenditure was increased to 117.3 and 118.7% of the predicted basal metabolic rate, according to Fleisch and to Harris and Benedict reference values, respectively (p less than 0.001). Furthermore, resting energy expenditure was increased to 120.8% of the predicted value according to body fat-free mass (p less than 0.001). This extra energy expenditure in patients with interstitial lung disease is similar to that recently reported in patients with chronic obstructive pulmonary disease.

Adult↗
PubMed2000

Pediatric origins of adult lung disease. 1. The contribution of airway development to paediatric and adult lung disease.

In summary, factors that affect airway growth early in development appear to cause physiological effects that can be persistent. Reduced airway function early in life does not necessarily result in persistent symptoms, but the long term effects and impact on the development of chronic airflow limitation in adults are yet to be determined. Generally, long term sequelae seem to be related to the severity of the initial insult, but the development of persistent increased bronchial responsiveness is an independent risk factor for symptoms and abnormal lung function in later life. In addition, there appear to be separate genetic factors that influence atopy, airway development, and bronchial responsiveness.

Adolescent↗
PubMedDate not supplied

Effect of lung volume reduction surgery in a rabbit model of bullous lung disease.

Clinical use of staple lung volume reduction surgery (LVRS) has proliferated for treatment of emphysema despite limited data regarding efficacy or optimal techniques. Recent studies in animal models of obstructive lung disease describe the decrease in lung compliance and increase in airway support as mechanisms of an improvement in pulmonary functions analogous to human data. We describe contrasting results in an animal model of bullous lung disease with a mixed but predominantly restrictive pattern of lung disease. Mixed restrictive and bullous lung disease was induced in 17 New Zealand white rabbits with i.v. Sephadex beads and endotracheally instilled carrageenan. Unilateral stapled lung volume reduction surgery was performed at 5 weeks postinduction of emphysema on the right lower lobe by lateral thoracotomy using a pediatric stapler. Static trans-pleural pressures were measured at 60, 40, and 20 cm3 inflation at preinduction (baseline), pre- and postoperatively, and 1 week postoperatively in anesthetized animals. Lungs were then harvested en bloc and examined histopathologically. The effects of volume reduction surgery on static lung compliance, lung conductance, and forced expiratory flows (FEF) were assessed. Five weeks after induction of lung disease, the animals had no significant change in static compliance and forced expiratory volume in 0.5 s (FEV0.5) or lung conductance compared to baseline. Immediately following LVRS, the animals showed a significant decrease in static compliance, FEV0.5, and conductance. One week postoperatively, compliance increased to approximately baseline levels along with a slight increase in FEFs and conductance toward preoperative levels. Histology examination revealed restrictive and bullous lung disease. Thus, we have demonstrated the feasibility of using an animal model for evaluation of volume reduction therapy for restrictive-obstructive lung disease. Physiologically, this model showed decrease conductance and decreased forced expiratory flows following lung volume reduction despite increased recoil. This is in contrast to increased conductance and flows seen in humans with severe emphysema following surgery and suggests that current criteria excluding patients with a significant restrictive component to their lung disease from LVRS surgery may be justified.

Animals↗
PubMed1998

The role of open lung biopsy in the management and outcome of patients with diffuse lung disease.

BACKGROUND: Open lung biopsy (OLB) has long been considered the gold standard for the diagnosis of parenchymal lung disease. With recent advances in computed tomographic imaging and diagnostic techniques (eg, bronchoscopy), we thought it necessary to reevaluate the role of OLB in the management of patients with interstitial lung disease. METHODS: We carried out a retrospective analysis of 103 OLBs performed at Hadassah University Hospital, Jerusalem, and Carmel Medical Center, Haifa, between 1980 and 1994. Data gathered included demographic information, underlying condition, indications for biopsy, diagnosis before biopsy, final diagnosis, change in therapy, and mortality. "Benefit" was defined as a change in therapy resulting in survival. RESULTS: There were 45 immunocompetent patients (group 1), 39 immunocompromised patients (group 2), and 26 children (group 3), 7 of whom were included in group 2 for analysis. Overall, a diagnosis was reached after OLB in 85% of patients. An unexpected diagnosis was reached in 52%, and a change in therapy was instituted in 46%. The overall mortality rate was 20%. In group 1, the mortality rate was 13%, and "benefit" from OLB was reached in only 18%. In group 2, the mortality rate was 39%, and "benefit" was achieved in 46%, and in group 3, the mortality rate was 12% and "benefit", 50%. CONCLUSIONS: Open lung biopsy is an excellent diagnostic technique. In immunocompetent patients, the "benefit" is relatively low, as therapy (corticosteroids) is frequently used after biopsy. In immunocompromised patients, therapy changes substantially after OLB, but mortality is high. Therefore, OLB should be reserved for patients in whom the diagnosis is likely to lead to a change in therapy and in patients in whom the underlying condition has a reasonable prognosis according to the clinical impression by the attending physician.

Adolescent↗
PubMed2002

Review: occupational and environmental lung disease.

Occupational and environmental lung disease is a vast topic. Therefore, this review focuses on areas that represent new clinical insights that have not been addressed recently in Current Opinion in Pulmonary Medicine. The topics are considered important for the future and emphasize diseases that strike large numbers of people or exposures that affect large segments of the population. This review highlights literature published between the years 2000 to 2001 related to air pollution, occupational asthma, lung diseases in agricultural workers, nylon flock workers lung disease, pneumoconiosis, and environmental exposure to biomass smoke, including environmental tobacco smoke. These publications highlight the changing world of occupational and environmental lung diseases. Traditionally, this field dealt with chronic diseases caused by very high levels of exposure to materials that affected virtually all workers to a similar degree. Disease could be recognized readily by characteristic symptoms, signs, and radiographic abnormalities. Dose-effect relationships were usually clear, and the solution to disease was generally to limit exposure for all workers. This approach served well for conditions such as coal workers pneumoconiosis or toxic responses to chlorine gas. The new world of occupational and environmental lung diseases often involves low levels of exposure to complex mixtures of materials that produce nonspecific or intermittent symptoms in a subgroup of exposed individuals. Interactions between genetic susceptibility, concomitant tobacco smoke exposure, and co-morbid diseases hugely complicate both diagnosis and prevention. New tools, and possibly new thought paradigms, are needed to detect, treat, and prevent occupational and environmental lung diseases in a changing world.

Asthma↗
PubMed2005

[Self assessment quality of life and lung diseases (SAQOL in patients with pulmonary carcinoma: influence to survival and impact of chronic obstructive pulmonary disease].

BACKGROUND: Lung cancer and chronic obstructive pulmonary disease (COPD) often occur concomitantly. Whilst there are several questionnaires relating to COPD that have been translated into German (CCOPDQ, CRQ, SGRQ) there is a need for a short instrument measuring the impact of the concomitant diseases or intervention on a patient's Quality of Life specifically in German language. As there is to date no genuine German questionnaire neither in general, nor in detail for both, lung cancer and the often concomitant COPD, we created and tested an appropriate single instrument. METHODS: The feasibility and validity of a short, self-administered quality of life questionnaire for use with patients diagnosed with COPD and/or pulmonary malignancies was evaluated. The 27 questions of Self Assessment Quality of Life in Lung Diseases (SAQOL) questionnaire were issued to out-patients with lung cancer (18 females, 75 males, mean 62.6 years, 18 to 81), 54 of with concomitant COPD. RESULTS: Correlations to comparable domains of the tumour-related QLQ-C30 of EORTC were good in cancer patients. Quality of life impact scores in the shorter and organ specific SAQOL domains showed even higher values than the QLQ C-30. A higher quote of Quality of life impaction was related to a poorer prognosis despite comparable tumour stages. There was a relevant impact related to the presence of COPD in addition to lung cancer. To investigate the validity in severe COPD an English version of the questionnaire was applied in the Respiratory Unit, Adelaide Australia, together with the Nottingham Health Profile in patients with long-term oxygen therapy (n = 20), which correlated well with the lung specific domains of SAQOL. CONCLUSION: We conclude that SAQOL is an easy to handle questionnaire, which shows on the one hand good correlation to the tumour-related domains of the broadly investigated and reliable QLQ C30, and on the other hand to the long-term used and valid lung specific generic Nottingham Health Profile in COPD. The important influence COPD in quality of life impact highlights the need for an organ specific questionnaire for both, lung cancer and obstructive airway disease. This important factor for quality of life alteration seems to be underestimated in other generic questionnaires or it needs the issue of at least two different and more time consuming instruments for adequate assessment. Additionally a high degree of quality of life impaction was linked to a short survival in our study patients with advanced lung cancer.

Humans↗
PubMed2004

Cardiac Troponin T levels and myocardial involvement in children with severe respiratory syncytial virus lung disease.

AIMS: To determine the prevalence of myocardial damage in severe respiratory syncytial virus (RSV) disease as evident from elevated cardiac Troponin T (cTnT) levels. To assess the nature of the myocardial involvement as manifested in electro- and echocardiographic abnormalities. To compare severity of disease with and without myocardial involvement as evident from duration of ventilation, inotrope requirements and death. METHODS: This was a prospective observational cohort study of children with RSV infection admitted to the paediatric intensive care unit at the Royal Liverpool Children's Hospital during the winter season 2002/2003. cTnT concentrations were measured using a third generation monoclonal sandwich immunoassay (Roche Diagnostics). RESULTS: 34 children were included in our study. 12 (35%) had elevated cTnT levels. The levels measured after admission had a median [interquartile range (IQR)] of 50 pg/ml (37.5-67.5). There was no significant difference (p > 0.05) between patients with and without elevated cTnT levels with regards to gender, gestational age at birth, history of neonatal intensive care, presence of congenital heart disease, chronic lung disease, inotrope requirements, duration of ventilation, death, fractional shortening on echocardiogram or arrhythmias. Children with elevated cTnT levels were significantly younger [median (IQR): 1.4 months (0.8-2.0)] than children without [median (IQR): 4.0 months (1.7-6.6)] (p = 0.04). The systolic blood pressure on admission was lower in children with increased cTnT compared to those with undetectable cTnT (p = 0.01). CONCLUSIONS: Myocardial involvement is common in infants with severe RSV lung disease without congenital heart disease. cTnT level elevation was associated with hypotension.

Child, Preschool↗
PubMed2005

Systemic tumor embolism mimicking gefitinib ('IRESSA')-induced interstitial lung disease in a patient with lung cancer.

We describe a 55-year-old man with advanced adenocarcinoma of the lung who received gefitinib ('IRESSA'). After gefitinib administration for 7 months, computed tomography scan of the chest demonstrated diffuse ground glass opacity and he was suspected to have developed gefitinib-induced interstitial lung disease (ILD). However, transbronchial lung biopsy (TBLB) revealed tumor cells in the middle-size lung vessels. Afterwards, multiple infarctions of the brain, spleen and left kidney were detected. Then, he was considered to have developed systemic tumor emboli, a rare complication. The clinical presentation of this patient was difficult to discriminate from that of ILD, and TBLB was useful in the differential diagnosis.

Adenocarcinoma↗
PubMed2006

Monitoring markers of disease activity for interstitial lung diseases with serum surfactant proteins A and D.

OBJECTIVES: Surfactant protein (SP) A and D are specific serum markers for interstitial lung diseases including idiopathic pulmonary fibrosis (IPF). The authors evaluated the critical roles of these markers on the prognoses of patients with IPF and the mechanisms of their elevation in sera. METHODOLOGY: The authors evaluated the relationship between prognosis and the serum markers in 82 IPF patients. The protein content and mRNA expression of the markers were evaluated using rats with interstitial pneumonia induced by bleomycin administration. RESULTS: Higher levels of serum SP-D at the time of the initial visit to the Sapporo Medical University Hospital were associated with poorer prognoses, while SP-A showed no significant affect on survival. Causes of the elevation in sera were due to the acceleration of, not only production in the lungs, leakage into the circulation. The elevation was associated with alveolitis but not fibrosis. CONCLUSIONS: SP-D is a good predictor of the prognosis in patients with IPF.

Animals↗
PubMed1999

Lung transplant waiting list: differential outcome of type of end-stage lung disease, one year after registration.

BACKGROUND: Donor lung scarcity, distinct natural courses of the different types of end-stage lung diseases, and lung allocation schemes demand appropriate candidate acceptance for a lung transplant and time of listing. This study was undertaken to investigate the association between type of end-stage lung disease and outcome, 1 year after a lung transplant candidate was put on the waiting list. METHODS: From 1990 to 1995, 1376 adult patients were registered for a first lung (n = 1006) or heart-lung (n = 370) transplantation in Eurotransplant. All patients were followed for at least 1 year. For each type of end-stage lung disease (cystic fibrosis, pulmonary fibrosis, emphysema, pulmonary hypertension, congenital heart disease, and other), chances of transplantation, of death on the waiting list, and of removal for other reasons, 1 year after listing, were calculated with the competing risks method. A multivariate Cox regression model was used to assess the influence of the type of end-stage lung disease on the waiting list outflow among other prognostic variables. RESULTS: Lung transplant candidates with emphysema and with pulmonary fibrosis had the highest chance of a transplant; however, patients with pulmonary fibrosis had also the highest probability of dying while waiting, while the emphysema patients and those with the type "other" had the lowest probability. In the multivariate analysis, the type of end-stage lung disease appeared as an independent prognostic factor for both outcomes. Compared to the patients with cystic fibrosis (reference group), only patients with pulmonary fibrosis had a significantly higher chance of a transplant (RR = 1.50); the lowest chance of death for the emphysema and the "other" patients was confirmed (RR = 0.53 and RR = 0.51, respectively). Recipient size, ABO blood group, country and epoch of listing also had a significant impact on the transplant chance, while country of listing and recipient age were the other factors independently influencing the chance of dying on the waiting list. On the heart-lung waiting list, the type of end-stage lung disease solely affected the chance of death prior to transplant. Compared with cystic fibrosis, pulmonary fibrosis had a significantly higher risk (RR = 2.93), closely followed by pulmonary hypertension (RR = 2.57). Factors crucial for the chance of a heart-lung transplant were recipient size, ABO blood group and country of listing. CONCLUSIONS: The type of end-stage lung disease is a distinctive factor for predicting survival on the lung and heart-lung transplant waiting list, and should be taken into account whenever assessing waiting list outcomes. When developing lung allocation schemes, it is medically justified to incorporate the type of end-stage lung disease.

Adolescent↗
PubMed2005

Lung transplantation and interstitial lung disease.

PURPOSE OF REVIEW: Interstitial lung disease includes a heterogeneous group of disorders that leads to respiratory insufficiency and death in a significant number of patients. Lung transplantation is a therapeutic option in select candidates. RECENT FINDINGS: The indications, transplant procedure options, and outcomes continue to evolve. Various recipient comorbidities influence the choice of procedure in patients with interstitial lung disease. Single lung transplants are used as the procedure of choice and bilateral transplants are reserved for patients with suppurative lung disease and patients with pulmonary hypertension. Issues unique to patients with interstitial lung disease affect the morbidity, mortality and recurrence of the disease. SUMMARY: Lung transplantation is an effective therapy for respiratory failure in interstitial lung disease with survival following transplant being similar to that achieved in transplant recipients with other diseases.

Comorbidity↗
PubMed1976

[Diagnosis of disseminated and localized lung diseases by means of transbronchial lung biopsy (author's transl)].

In 61 patients with mostly diffuse lung diseases 64 transbronchial lung biopsies have been performed by means of rigid biopsy forceps in general anesthesia. 31 of the 36 pathological bioply specimens were diagnostically helpful or represented the clinical diagnosis. Complications were moderate bleeding in three cases and pneumothorax (3 cases). One patient died after myocardial reinfarction occuring under general anesthesia. Transbronchial lung biopsy is indicated when routine methods fail to establish the diagnosis of pulmonary lesions, particularly in patients having higher operative risks. More use of the transbronchial forceps biopsy is expected to improve the diagnostic yield, especially in patients with miliary pulmonary lesions.

Biopsy↗