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PubMed1990

Assessment of rebreathing O2 consumption in humans with normal and diseased lungs.

We investigated sources of error in estimating steady-state O2 consumption (VO2ss) by calculating O2 uptake from an anesthesia bag containing O2, He, and N2 during 10-20 s of rebreathing (VO2rb). In 11 normal resting subjects, VO2rb calculated with end-tidal sampling overestimated VO2ss by 16 +/- 15% (SD) (P less than 0.003). This error was proportional to the increase in pulse rate during rebreathing, so that pulse-corrected VO2rb slightly underestimated VO2ss by 2.1 +/- 12.2% (P = 0.66) in the six subjects who rebreathed 28% O2 in the rebreathing bag but significantly underestimated VO2ss by 7.5 +/- 6.7% (P less than 0.04) in the six subjects who rebreathed 21% O2 in the rebreathing bag. During exercise, VO2rb underestimated VO2ss by 4 +/- 12% (P less than 0.001) and by 7 +/- 6% at O2 consumptions greater than 2,000 ml/min if O2 in the rebreathing bag was kept above 20% throughout rebreathing. We found that VO2rb calculated with end-tidal gas concentrations underestimated VO2ss by 1-43% in patients with moderate-to-severe obstructive lung disease, with even greater errors when mixed expired samples were used. The magnitude of the discrepancy correlated poorly with abnormalities in standard pulmonary function tests. Based on these data, VO2rb closely approximates VO2ss in normal subjects, provided hypoxia during rebreathing is avoided and cardiac acceleration from rebreathing is taken into account during resting measurement.

Adult↗
PubMed2001

Dynamic spiral MRI of pulmonary gas flow using hyperpolarized (3)He: preliminary studies in healthy and diseased lungs.

An optimized interleaved-spiral pulse sequence, providing high spatial and temporal resolution, was developed for dynamic imaging of pulmonary ventilation with hyperpolarized (3)He, and tested in healthy volunteers and patients with lung disease. Off-resonance artifacts were minimized by using a short data-sampling period per interleaf, and gradient-fidelity errors were compensated for by using measured k-space trajectories for image reconstruction. A nonsequential acquisition order was implemented to improve image quality during periods of rapid signal change, such as early inspiration. Using a sliding-window reconstruction, cine-movies with a frame rate of 100 images per second were generated. Dynamic images demonstrating minimal susceptibility- and motion-induced artifacts were obtained in sagittal, coronal, and axial orientations. The pulse sequence had the flexibility to image multiple slices almost simultaneously. Our initial experience in healthy volunteers and subjects with lung pathology demonstrated the potential of this new tool for capturing the features of lung gas-flow dynamics.

Helium↗
PubMed2001

Unusual systemic disorders associated with interstitial lung disease.

Interstitial lung disease often starts as a reaction to a causative insult or antigen, such as an inhaled environmental organic or inorganic dust and autoimmune mediated injury. When no underlying cause can be found, the inflammatory change in the gas exchanging parts of the lungs and associated fibrosis is called idiopathic pulmonary fibrosis (cryptogenic fibrosing alveolitis). The common causes of pulmonary fibrosis can be classified as granulomatosus, nongranulomatous, neoplastic, and iatrogenic. There are other multisystem disorders not included in this classification that are associated with interstitial lung disease. Amyloidosis, Behcet disease, Kikuchi disease, and Whipple disease are such multiorgan disorders that involve the lungs.

Amyloidosis↗
PubMed2000

Strategies for prevention of neonatal chronic lung disease.

Chronic lung disease (CLD) of prematurity remains a substantial problem despite modern perinatal and neonatal care. CLD remains related to gestational age and lung immaturity, although it has become clear that severe initial lung disease is not a prerequisite for CLD to develop. Attempts to prevent CLD to date have not adequately addressed the multifactorial nature of the complex pathophysiology that leads to CLD. Thus, results have been modest at best. Prevention of CLD will require a multifaceted approach with specific interventions and care practices focused on different aspects of the pathway that leads to CLD. This review considers new information related to causation of CLD and the magnitude of the effect of prevention strategies tested to date. This article also advances the hypothesis that CLD is preventable with a global strategy of minimizing inciting events, optimizing management, and specific therapies aimed at intrinsic vulnerabilities.

Anti-Inflammatory Agents↗
PubMed2007

Expression profiling in granulomatous lung disease.

Granulomatous lung diseases, such as sarcoidosis, hypersensitivity pneumonitis, Wegener's granulomatosis, and chronic beryllium disease, along with granulomatous diseases of known infectious etiologies, such as tuberculosis, are major causes of morbidity and mortality throughout the world. Clinical manifestations of these diseases are highly heterogeneous, and the determinants of disease susceptibility and clinical course (e.g., resolution vs. chronic, progressive fibrosis) are largely unknown. The underlying pathogenic mechanisms of these diseases also remain poorly understood. Within this context, these diseases have been approached using genomic and proteomic technologies to allow us to identify patterns of gene/protein expression that track with clinical disease or to identify new pathways involved in disease pathogenesis. The results from these initial studies highlight the potential for these "-omics" approaches to reveal novel insights into the pathogenesis of granulomatous lung disease and provide new tools to improve diagnosis, clinical classification, course prediction, and response to therapy. Realizing this potential will require collaboration among multidisciplinary groups with expertise in the respective technologies, bioinformatics, and clinical medicine for these complex diseases.

Gene Expression Profiling↗
PubMedDate not supplied

The quality of life of carers of patients with severe lung disease.

Severe lung disease is known to affect the lives of not only the sufferer but also his/her family. This qualitative phenomenological study identified seven patients with severe lung disease and studied the quality of life of their carers (five female, two male) who were not fully employed, living in the same house or nearby. In a semi-structured interview, the carers were asked about looking after their spouse or relative, whether they had support and the effect of caring on their health and finances. The findings showed the carers' lives to be severely restricted, all carrying a heavy emotional burden of frustration, depression and isolation: part-time jobs were important both financially and to reduce isolation. Family support was vital to their coping, but few had received professional help. All were affected by reduction in income, but claiming allowances was confusing; unpredictability of the disease complicated much-needed recreation and holidays. Findings were similar to previously published data.

Adaptation, Psychological↗
PubMed2001

The importance of balanced pro-inflammatory and anti-inflammatory mechanisms in diffuse lung disease.

The lung responds to a variety of insults in a remarkably consistent fashion but with inconsistent outcomes that vary from complete resolution and return to normal to the destruction of normal architecture and progressive fibrosis. Increasing evidence indicates that diffuse lung disease results from an imbalance between the pro-inflammatory and anti-inflammatory mechanisms, with a persistent imbalance that favors pro-inflammatory mediators dictating the development of chronic diffuse lung disease. This review focuses on the mediators that influence this imbalance.

Anti-Inflammatory Agents↗
PubMedDate not supplied

Bronchoscopy in diffuse lung disease: evaluation by open lung biopsy in nondiagnostic transbronchial lung biopsy.

Transbronchial lung biopsy through the flexible bronchoscope is used widely for the diagnosis of diffuse lung disease; however, a significant number of specimens obtained by the bronchoscopic 2-mm biopsy forceps will reveal nonspecific findings, eg, interstitial fibrosis or nonspecific pneumonitis. Such a report may be an accurate reflection of the presence of idiopathic pulmonary fibrosis or nonspecific pneumonitis, but may merely indicate that the true diagnosis has been missed. We retrospectively studied 38 patients with diffuse lung disease whose transbronchial lung biopsies yielded nonspecific abnormalities. Subsequently, these patients were subjected to open lung biopsies. Nineteen of the 38 patients (50%) had a specific diagnosis made by open lung biopsy. The diagnoses included bronchiolitis obliterans, alveolar proteinosis, metastatic carcinoma, lymphoma, tuberculosis, and bronchioloalveolar cell carcinoma. Although transbronchial lung biopsy is useful in the diagnosis of many diffuse lung diseases, it is not a replacement for open lung biopsy. When nonspecific findings by transbronchial lung biopsy do not correlate with the clinical picture, open lung biopsy should be performed.

Adolescent↗
PubMed1994

The relationship of pulmonary interstitial emphysema to subsequent type of chronic lung disease.

Chronic lung disease of prematurity (CLD) can be classified using the chest radiograph taken on day 28 into type 1 (homogeneous opacification) or type 2 (the presence of cystic change) and it has been suggested that the presence of pulmonary interstitial emphysema (PIE) leads to the development of type 2 CLD. To further study this relationship we examined the chest radiographs taken on days 1-7, 14, 21 and 28, of 202 infants treated at Liverpool Maternity Hospital between January 1980 and December 1989 who developed CLD. 39% (54/137) of infants who developed type 1 CLD had suffered from PIE compared with 78% (51/65) with type 2 CLD (p < 0.001). There was no difference in the incidence of PIE in infants who developed CLD and subsequently died compared with those who survived. In the infants who survived there was no significant difference in length of oxygen dependency between those who suffered from PIE (median 99 days oxygen dependent) and those who had no PIE (median 105 days). We conclude that the presence of PIE is associated with subsequent development of type 2 CLD but is not a prerequisite for this radiographic type of chronic lung disease. Of those infants who survive to develop CLD, the presence of PIE does not alter prognosis in terms of duration of oxygen dependency or mortality.

Chronic Disease↗
PubMed1978

Occupational lung disease.

Occupational lung diseases can be conveniently classified into disorders of the airways, the alveoli, and the lung interstitium. Diseases of each category have a distinct clinical and pathologic presentation despite diverse causes.

Asthma↗
PubMed1994

[Paradoxical respiration in patients with chronic diffuse lung diseases and regional lung rheography for its diagnosis].

The paper shows that some patients with disseminated pneumo- and pleurofibrosis and pulmonary emphysema, which have developed in chronic specific and nonspecific lung diseases, have severe local disorders of respiratory biomechanics, which appear as the paradoxical ventilation phenomenon It also indicates that these abnormalities can be identified by the rather easy-to-use and accessible technique, regional rheography of the lung. The significance of detection of the paradoxical local ventilation phenomenon for clarifying the mechanism responsible for ventilation disorders is illustrated by a clinical note.

Adult↗
PubMed2005

Pediatric interstitial lung disease masquerading as difficult asthma: management dilemmas for rare lung disease in children.

Idiopathic nontransplant-related childhood bronchiolitis obliterans is an uncommon disease. Most patients present with chronic recurrent dyspnea, cough and wheezing, which are also features of asthma, by far a much more common condition. The present case study reports on a six-year-old girl who presented to a tertiary care centre with recurrent episodes of respiratory distress on a background of baseline tachypnea, chronic hypoxemia and exertional dyspnea. Her past medical history revealed significant lung disease in infancy, including respiratory syncytial virus bronchiolitis and repaired gastroesophageal reflux. She was treated for 'asthma exacerbations' throughout her early childhood years. Bronchiolitis obliterans was subsequently diagnosed with an open lung biopsy. She did not have sustained improvement with systemic corticosteroids, hydroxychloroquine or clarithromycin. Cardiac catheterization confirmed the presence of secondary pulmonary hypertension. Treatment options remain a dilemma for this patient because there is no known effective treatment for this condition, and the natural history is not well understood. The present case demonstrates the need for careful workup in 'atypical asthma', and the urgent need for further research into the rare lung diseases of childhood.

Asthma↗
PubMed2001

Classifying interstitial lung diseases in a fractal lung: a morphologist's view "anno Domini 2000".

Interstitial lung diseases (ILDs) remain a challenging problem for the pathologist. New insights in aetiology and pathogenesis, new diagnostic tools and successful research have led to a renewed interest in ILDs during the last few years, and highlighted the need for a novel classification, particularly of the chronic and/or idiopathic categories of interstitial pneumonias. The present paper compares the terminology of the latter categories in current and previous classifications and briefly discusses the pathological basis for the classifications of ILDs in general, and for the idiopathic interstitial pneumonias (IIPs) in particular. The difference between high versus low morphological specificity determines the pathological classifications. The classification of lIPs relies upon a pattern recognition taking temporal and spatial distribution into consideration. The last section of this paper discusses recent research opposing the conventional pathological approach, analogous to the mechanical two-compartment model of the lung, in which a discontinuity is considered between these two compartments, and thus, a distinction is made between interstitial lung diseases with and without bronchiolitis. In the recent "fractal" concept, the continuity of the lung architecture is emphasized: the lung is a so-called fractal tree with noninteger dimensions. In this fractal model, an interstitial lung disease effects a peripheral part of the pulmonary fractal tree and this may or may not include bronchioles.

Bronchiolitis↗
PubMed2002

Matrix metalloproteinases in lung diseases.

Matrix metalloproteinases (MMPs) are a pivotal family of zinc enzymes responsible for degradation of the extracellular matrix (ECM) components including basement membrane collagen, interstitial collagen, fibronectin, and various proteoglycans, during normal remodeling and repair processes. The potent proteolytic activities of MMPs is mainly regulated by the balance with specific tissue inhibitors of Matrix metalloproteinases (TIMP). Excessive or inappropriate expression of MMP may contribute to the pathogenesis of tissue destructive processes in a wide variety of diseases including lung diseases. Although the precise mechanisms are still unknown, the contribution of individual MMPs are worth investigating in seeking the pathogenesis of various lung diseases such as lung cancer, bronchial asthma, chronic obstructive pulmonary disease, acute lung injury, pulmonary hypertension and interstitial lung diseases. In particular, the close association of each lung disease with the destructive effects of gelatinase A and B (also called MMP-2 and MMP-9) on the basement membrane in early alveolar remodeling, and that of collagenase-1 (MMP-1) on the major interstitial structural protein of ECM have received considerable attention. The interaction of MMPs with chemical mediators and inflammatory cytokines has also been reported in some recent studies. Several promising therapeutic approaches to inhibit MMPs have just started in the field of oncology, while more specific MMP inhibitors may be required for further investigation in other fields of lung diseases. In this review, the main focus is on the recent clinical and experimental findings and the contributions of MMPs and/or TIMPs in the lung diseases.

Extracellular Matrix↗
PubMed1982

[Occupation-related lung diseases in hard metal production and manufacturing. An allergic process?].

The clinical heterogeneity of hard metal disease lung with its two basic forms, i.e. hart metal pneumonitis and hard metal asthma, supports the view of different pathogenetic mechanisms. Cobalt, which is generally considered the noxious agent in hard metal diseases, is cytotoxic on the one hand and allergenic on the other. Four typical, extensively investigated cases are presented, i.e. hard metal pneumoconiosis, hypersensitivity pneumonitis, toxic-irritative hard metal asthma and allergic cobalt asthma. The immunological results were negative in the patient with hard metal pneumoconiosis. A hard metal grinder with typical occupational hypersensitivity pneumonitis showed a high level of precipitating antibodies against Aureobasidium pullulans, a well-known antigen in humidifier fever and sequoiosis. The inhalative provocation test induced on both patients with hard metal asthma an immediate and prolonged, i.e. a dual asthmatic reaction. Only the patient with allergic contact eczema due to cobalt and a positive epicutaneous test of the delayed type and a positive scratch tests of the immediate type with cobalt chloride.

Adult↗
PubMed2003

[Interstitial lung diseases].

Interstitial lung diseases (ILD) are an heterogeneous group of inflammatory diseases characterized by an anatomical distortion of peripheral airways and interstitium, determined by a first stage of alveolitis and a following stage of fibrosis. Natural history of several ILD is characterized by slow and progressive destruction of alveolar-capillary functional units, often with respiratory failure and death. For their smoldering evolution and not specificity of symptoms (exertional dyspnea and cough) ILD may remain not diagnosed and not treated for a long time.

Adrenal Cortex Hormones↗