Interstitial Lung Research Articles

Hipertensión arterial pulmonar en paciente con neumonía intersticial no específica y con test de vasorreactividad positivo

Pulmonary hypertension (PH) is a disease characterized by a progressive increase of pulmonary vascular resistance, which gives rise to right ventricular failure and premature death. This may be idiopathic or be associated to different conditions, standing out among them collagen, toxic diseases and lung conditions such as interstitial lung diseases.We present the case of a female patient diagnosed of PH with images suggestive of interstitial disease in the high resolution computed tomography and who was subsequently diagnosed of a non-specific interstitial pneumonia. It is important to stress the positive vasoreactivity test in cardiac catheterization that may indicate the presence of two independent conditions in the present case.

The importance of correction for tissue fraction effects in lung PET: preliminary findings

It has recently been recognized that PET/CT may play a role in diffuse parenchymal lung disease. However, interpretation can be confounded due to the variability in lung density both within and between individuals. To address this issue a novel correction method is proposed. A CT scan acquired during shallow breathing is registered to a PET study and smoothed so as to match the PET resolution. This is used to derive voxel-based tissue fraction correction factors for the individual. The method was evaluated in a lung phantom study in which the lung was simulated by a Styrofoam/water mixture. The method was further evaluated using (18)F-FDG in 12 subjects free from pulmonary disease where ranges before and after correction were considered. Correction resulted in similar activity concentrations for the lung and background regions, consistent with the experimental phantom set-up. Correction resulted in reduced inter- and intrasubject variability in the estimated SUV. The possible application of the method was further demonstrated in five subjects with interstitial lung changes where increased SUV was demonstrated. Single study pre- and post-treatment studies were also analysed to further illustrate the utility of the method. The proposed tissue fraction correction method is a promising technique to account for variability of density in interpreting lung PET studies.

Claudin-4 Levels Are Associated with Intact Alveolar Fluid Clearance in Human Lungs

The removal of edema from the air spaces is a critical function of the alveolar barrier requiring intact tight junctions. Alveolar fluid clearance contributes to graft function after transplantation and is associated with survival in patients with acute lung injury. Claudin-4 concentrations are known to increase during lung injury and the loss of claudin-4 decreases alveolar fluid clearance in mice. This study was therefore undertaken to evaluate whether differences in lung expression of the tight junction protein claudin-4 are associated with alveolar fluid clearance or clinical measures of lung function. Alveolar fluid clearance rates were measured in ex vivo perfused human lungs not used for transplantation and were compared with histological lung injury and clinical measures of lung injury in the donors. Claudin-4 staining demonstrated a positive correlation with alveolar fluid clearance (Spearman rank correlation [r(s)] = 0.71; P < 0.003); however, claudin-4 staining was not strongly associated with histological measures of lung injury. The expression of other tight junction proteins (including ZO-1) was not associated with alveolar fluid clearance or claudin-4 levels. Claudin-4 staining was lower in lungs from donors with greater impairment in respiratory physiology. These data suggest that claudin-4 may promote alveolar fluid clearance and demonstrate that the amount of claudin-4 expressed may provide specific information regarding alveolar epithelial barrier function that strengthens the link between histological changes and physiological impairment.

Clinical analysis of nineteen elderly patients with rheumatoid arthritis

Objective To investigate the clinical features of rheumatoid arthritis (RA) in the aged.Methods The clinical features and inflammatory index of 19 aged patients with RA were retrospectively analyzed and compared with those of 103 young patients with RA. Results The acute onset was ocurred in 11 cases in EORA group(11/19,57.9%) ,32 cases in MRA group (32/103,31.1%), there was sighicant difference two groups (P ＜0. 05). There were 10 cases with intertitial lung disense in EORA group(52.6%) ,27 cases(26.2%) in MRA group.There were no statistical differenes between two groups in erythrocyte sedimentation rate, rheumatoid factor, c-reactive,EORA incidence rate in male and female. Conclusions In comparison with MRA group,the onset of disease in patients of EORA group was more acute than that of MRA,it had higher degree of disease activity. The commonly seen extra-joint manifestation were feeble and interstitial disease lung. Early diagnosis and treatmentof EORA was favor for the prevention of deterioration of this disease. Key words: Arthritis,rheumatoid; Disease attributes; Aged

Recent consumption of a large meal does not affect measurements of lung function

It is currently recommended that patients avoid large meals prior to their lung function tests. The aim of this study is to determine whether this recommendation is necessary in clinical practice. A randomized controlled cross-over trial was conducted. Subjects performed lung function tests (spirometry, measurement of lung volumes and gas transfer) prior to, directly following and 2 h after consuming a large breakfast. On the control arm, subjects performed the same lung function tests while fasting for the duration of the morning. The study subjects comprised 12 healthy subjects, 10 COPD patients and 10 patients with interstitial lung disease. There were no significant differences between measurements on the meal and control days for FEV(1), FVC, TLC or DL(CO). There were no significant changes with time in any of these parameters over the course of either the meal or control morning. Common measures of lung function are not affected by the prior consumption of a large meal and it is unnecessary to advise patients to avoid a large meal prior to lung function assessment.

An open-label expanded access study of lapatinib and capecitabine in patients with HER2-overexpressing locally advanced or metastatic breast cancer

BackgroundThe Lapatinib Expanded Access Program (LEAP) was designed to provide access to lapatinib plus capecitabine for HER2-positive metastatic breast cancer patients who previously received an anthracycline, a taxane, and a trastuzumab and had no other treatment options. Patients and methodsLEAP opened globally and enrollment continued until lapatinib received regulatory approval in each participating country. Patients were assessed for progression-free survival (PFS) and overall survival (OS) and monitored for serious adverse events (SAEs). ResultsAs of 30 September 2008, 4283 patients from 45 countries enrolled in LEAP. The median treatment duration was 24.7 weeks. The most common drug-related SAEs were diarrhea (9.7%), vomiting (4.3%), and nausea (2.4%) and were mainly grade 3 or higher. The incidences of special interest SAEs were decreased left ventricle ejection fraction (0.5%), interstitial lung disease/pneumonitis (0.2%), and serious hepatobiliary events (0.4%). This safety profile is consistent with the overall lapatinib program. The median PFS and OS were 21.1 [95% confidence interval (CI) = 20.1–22.3] and 39.6 (95% CI = 37.7–40.7) weeks, respectively (n=4006). Subgroup analysis showed longer PFS and OS in patients who had not received prior capecitabine. ConclusionsThese results demonstrate the safety and efficacy of lapatinib in a broader patient population compared with a clinical trial.

Superoxide production by neutrophils in patients with interstitial and other lung diseases

Superoxide production by neutrophils in patients with interstitial and other lung diseases

An electron microscopic study of the pulmonary alveolar capillaries in idiopathic interstitial pneumonia and lungs of collagen vascular diseases

The ultrastructure of pulmonary alveolar capillaries in idiopathic interstitial pneumonia (IIP) and collagen vascular diseases (CVD) were investigated. In IIP, the endothelial cells were only slightly swollen. The basement membrane (BM) was moderately thickened. In CVD, swelling of the endothelial cells and thickening of the BM were more severe than those of IIP. The injury of the endothelial cells seemed to be more severe than IIP. The patients with PSS and MCTD revealed degeneration of endothelial cells as well as lamellation of BM. The endothelial cell damage was most severe among CVD cases, and these changes were assumed to induce pulmonary hypertension. Microtubular structures were observed in the endothelium of SLE, dermatomyositis, polymyositis, PSS and MCTD patients. Weibel-Palade bodies and increase of pericytes were noticed in PSS and MCTD patients which seemed to be related to endothelial injuries. No electron-dense deposits were observed in any case.

Etiological examination of idiopathic interstitial pneumonia and lung cancer in autopsy cases

In order to investigate the etiology of usual interstitial pneumonia (UIP) and UIP with lung cancer (LC), autopsy findings in 18 cases of UIP with LC and 11 cases of uncomplicated UIP were clinicopathologically compared with the environmental factors of smoking habits and occupation. UIP with LC was highly correlated with smoking, especially heavy smoking and with occupations in which dust is inhaled, such as electrical installation and ceramic production, indicating that these environmental factors are important background factors in the complication of UIP with IC. Pathologic examination of cases of UIP with LC (6 squamous cell carcinomas, 5 small cell carcinomas, 4 adenocarcinomas, and 3 large cell carcinomas, 2 of which showed pulmonary double carcinoma revealing a slight correlation between fibrosis and primary site of LC and a slightly greater correlation of squamous cell carcinoma and small cell carcinoma to smoking habits and inhalation of dust. In terms of the correlation between UIP and LC among autopsy cases, the environmental factors proved to be more significant than the fibrotic findings. These environmental factors are thought to merit consideration as common predisposing factors in the development of LC and its complication with UIP.

Interstitial pneumonitis following intrapleural chemotherapy

BackgroundMucinous neoplasms within the abdomen may disseminate by direct extension through the diaphragm to involve the pleural space. Treatment of this condition is by parietal and visceral pleurectomy followed by hyperthermic intrapleural chemotherapy.Case presentationIn this case report a patient developed persistent right upper lobe interstitial pneumonitis and progressive parenchymal fibrosis following intrapleural chemotherapy treatment with mitomycin C and doxrubicin. The condition persisted until death 28 months later. Death was from progressive intraabdominal disease with intestinal obstruction and sepsis associated with progressive pulmonary parenchymal disease. The right pleural space disease did not recur.ConclusionThis manuscript is the first case report describing interstitial pneumonitis and lung fibrosis following intrapleural chemotherapy. Since pulmonary toxicity from chemotherapy is a dose-dependent phenomenon, dose reduction of intrapleural as compared to intraperitoneal hyperthermic chemotherapy may be necessary.

Particokinetics and Extrapulmonary Translocation of Intratracheally Instilled Ferric Oxide Nanoparticles in Rats and the Potential Health Risk Assessment

Exposure to nanoparticles has presented potential risks to human cardiorespiratory systems. Pulmonary retention and extrapulmonary redistribution of inhaled nanoparticles have been considered to be important contributing factors of cardiorespiratory diseases. In the present work, 22-nm (59)Fe(2)O(3) nanoparticles (radioactive isotope (59)Fe-labeled ferric oxide nanoparticles) were intratracheally instilled into the male Sprague-Dawley rats at a dose of 4 mg/rat. Extrapulmonary distribution of (59)Fe(2)O(3) in organs and its metabolism in lung, blood, urine, and feces were measured for 50 days of exposure. Phagocytosis and clearance of agglomerated nano-Fe(2)O(3) by monocytes/macrophages were observed by histopathology and inductively coupled plasma-mass spectrometry examination. Our results showed intratracheal-instilled nano-(59)Fe(2)O(3) could pass through the alveolar-capillary barrier into systemic circulation within 10 min that consisted with one-compartment kinetic model. The nano-(59)Fe(2)O(3) in the lung was distributed to organs rich in mononuclear phagocytes, including liver, spleen, kidney and testicle. The plasma elimination half-life of nano-(59)Fe(2)O(3) was 22.8 days and the lung clearance rate was 3.06 microg/day, indicating the systemic accumulation and lung retention had occurred. The deposited nano-Fe(2)O(3) in interstitial lung was probably contributed by the particles escaping from alveolar macrophages phagocytosis and macrophages clearance function overloading. Our results suggest that the effect of Fe(2)O(3) nanoparticles exposure, even at low concentration, should be assessed because of the potential lung and systemic cumulative toxicity of the nanoparticles.

Improved clinical and cell cycle response with an mTOR inhibitor, daily oral RAD001 (everolimus) plus letrozole versus placebo plus letrozole in a randomized phase II neoadjuvant trial in ER+ breast cancer

530 Background: Activation of the mTOR pathway is a key adaptive change driving endocrine resistance. RAD001, an oral mTOR inhibitor, and letrozole synergistically inhibit proliferation in breast cancer cells. Methods: 270 postmenopausal women with > T2 ER+ tumors were randomized to receive 4 mo of letrozole 2.5mg QD + RAD001 10mg QD or letrozole 2.5mg plus placebo. The primary endpoint was overall clinical response. Mandatory needle biopsies were collected immediately prior to initial treatment, and at day 15 after treatment initiation. Samples were assessed at baseline for Her2 by FISH and mutation of exons 9 and 20 of PIK3CA and exons 5–8 of TP53, and at baseline and day 15 for Ki67, phospho-Akt S473, phospho-S6, PTEN, CyclinD1, ER, PR, p53, and total Akt and S6 by immunohistochemistry. A total of 207 patients (77%) were primary marker evaluable and clinical outcome evaluable; 186 patients had an evaluable second biopsy. Results: The clinical response rate with RAD001 + letrozole was significantly superior to letrozole alone at the preplanned Alpha of 0.1 (68 vs 59%, p=0.062). This was confirmed by ultrasound (OR 58% vs 47 %, p=0.035). Pharmacodynamic changes in each treatment arm were observed. Marked downregulation in progesterone receptor and cyclin D1 were seen in response to letrozole. Phospho- S6 levels showed dramatic down-regulation only in response to RAD001. Cell cycle response, as defined by either % reduction in Ki67 at day 15 or by proportion of patients with Ki67≤2 at day 15, was also significantly higher in the RAD001 + letrozole arm (57% vs 30% for Ki67≤2 at day 15, p<0.01). The rate of grade 3/4 adverse events (Aes) was 22.6% in the RAD001 + letrozole arm vs 3.8% in the placebo + letrozole arm. Most frequent grade 3/4 Aes with RAD001 + letrozole were hyperglycemia (n=7), stomatitis (3), interstitial lung disease/pneumonitis (3) and infections (3). Conclusions: RAD001 significantly increases the efficacy of letrozole in newly diagnosed ER+ breast cancer, with regard to both clinical and cell cycle response. The increased cell cycle response rate in the RAD001 arm was found in all subsets of tumors, including PTEN-positive, PIK3CA wild-type tumors. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Novartis Novartis Novartis Novartis Novartis

Histiocytosis X: Klinik und Verlauf bei fünf Patienten

Histiocytosis X developed in five patients (one woman and four men) when aged between 15 and 44 years. The initial sign in four of them was eosinophilic granuloma of the bone, in one it was pulmonary involvement. In three patients the disease remained confined to bone, while in two it involved the lungs and central nervous system, respectively. Osteolysis regressed spontaneously in one of the men, while in the woman there has been no recurrence 8 years after resection of the focus. In another man an osteolytic focus in a rib was noted after a 9-year recurrence-free interval. The man with pulmonary and bone involvement received chemotherapy with vinblastine and prednisone: dyspnoea and cough disappeared, vital capacity improved and the interstitial lung changes regressed. The osteolytic foci were repeatedly irradiated in the man with bone and CNS involvement. This brought about considerable reduction in pain but no significant radiological changes of the foci. Two courses of chemotherapy were given over 12 years, once with vincristine and prednisone, afterwards with cyclophosphamide. This arrested the progression of the osteolytic foci, but each time they recurred when the drugs were stopped.

RTK-based vaccines elicit specific CD8+ T cell responses in HLA-A2 transgenic mice (48.1)

Abstract Many receptor tyrosine kinases (RTK) are overexpressed/dysregulated in advanced cancers, serving as negative prognostic indicators. We evaluated the immunogenicity of dendritic cell (DC)/RTK(EphA2, EGFR, Her2/neu)-based vaccines in HLA-A2 (HHD) Tg mice. To enhance the stimulatory capacity of BM-derived DCs, these cells were infected with a recombinant adenovirus encoding mIL-12p70 (Ad.IL12), prior to being pulsed with RTK-derived peptides. We also evaluated a cohort of DC co-infected with both Ad.IL12 and Ad.EphA2. Each of these DC preparations (vs. control DCs) were injected three times s.c. into HHD mice on a weekly schedule. DTH reactions were monitored 48–72h after each vaccination and splenocytes were harvested on d28 and d60 to assess specific CD8+ T cell reactivity (IFN-γ ELISA). Autoimmunity pathology in RTK+ normal tissues (i.e. kidney, liver, lung) were also evaluated for immune infiltration and tissue destruction by (immuno)histochemistry. Vaccines induced specific DTH responses and Tc1 responses in HHD mice, in association with an increased accumulation of CD8+ T cells around proximal endothelial cells (PEC) in the kidney and in the interstitial lung at d28, in the absence of tissue pathology. DC/RTK-based vaccines may promote specific Type-1 immunity that has the potential to eradicate RTK+ tumors, while sparing normal RTK+ tissues. This work was supported by NIH R01 grant CA114071 (W.J.S.)

Endothelial Permeability and 3-Nitrotyrosine in Major Burns

AbstractIn patients with extensive burns microvascular hyperpermeabi-lity occurs not only at the injured sites but also in regions distantfrom the injury. The mechanism of this burn oedema is still notcompletely understood, nor why it stops after 18–36 hours.However, there is increasing evidence that an overwhelmingproduction of reactive oxygen and nitrogen species (ROS/RNS)plays an important role in this context. Our data document thegeneration of peroxynitrite (ONOO ) by detection of its footprint3-nitrotyrosine in thermally injured human skin. The immuno-histological detection reveals the location of 3-nitrotyrosine atthe endothelium and further adds to the hypothesis of oxidative/nitrosative stress. A promising therapeutic approach might behigh-dose antioxidant treatment as the enhanced free radicalproduction in burn trauma is paralleled by impaired antioxidantmechanisms. The most promising results for the reduction ofoedema formation and decreased early resuscitation fluid vo-lume are known for intravenous vitamin C treatment. This papergives a short review of the literature on this topic.Key wordsCapillary leak oedema iNOS reactive oxygen/nitrogenspecies vitamin CIntroductionIn patients with extensive burns – defined as a burn size of morethan 30% total body surface area (TBSA) – microvascular hyper-permeability occurs not only at injured sites but also in regionsdistant from the injury [29,33,42]. This leads to significant fluidand protein leakage from the intravascular space to the inter-stitial space. Cardiac output and tissue perfusion are reduced, sohypovolemic shock and generalised oedema formation are theclinically dominant symptoms in the early phase of the burntrauma [12,38]. Treatment approaches of major burns includemassive resuscitation fluid volume (4mL/kg % TBSA accordingto the Parkland formula) during the first 24 hours after burninjury [40]. While this aggressive post-burn volume replacementincreases oxygen delivery to previously ischaemic tissue, it alsogenerates excess volume accumulation in the interstitial spaceand lungs and is thought to initiate a series of deleterious eventsby reperfusion of previously ischaemic tissue [12,33].There is increasing evidence that oxidative stress plays an im-portant role in the development of capillary leakage after majorburn injury and is associated with the secondary damage totissues distant from the injured skin [2,12,18–20,25,41]. Inischaemic tissue ATP (adenosine triphosphate) levels graduallyfall and increased AMP (adenosine monophosphate) is convertedto hypoxanthine. This provides the substrate for xanthine oxi-dase and is one source for the production of reactive oxygenspecies (ROS) [12]. Activated neutrophils produce free radicals inthe development of profound inflammation [5,27]. As free radi-cals are too short-lived to be measured directly, characteristic

Interleukin-8 Expression in Lung Tissue During Ischemia-Reperfusion

Local cytokine production is a pathogenic factor in ischemia-reperfusion injury in early graft dysfunction. This study analyzed interleukin 8 (IL-8) messenger RNA (mRNA) expression in lung tissue and the association between IL-8 mRNA levels and interstitial lung changes in an experimental model of warm lung ischemia-reperfusion. We studied 16 New Zealand rabbits divided into 3 groups: control, ischemia (tissue taken from right lower lobe after 1, 2, or 3 hours of ischemia), and reperfusion (tissue taken from right upper and middle lobes after 1 hour of ischemia and 1, 2, or 3 hours of reperfusion). Expression of IL-8 mRNA was determined by reverse transcription and polymerase chain reaction. Interstitial infiltration by polymorphonuclear neutrophils was determined. The Mann-Whitney U-test was used for statistical comparisons, with P< .05 considered to indicate a significant result. During ischemia, IL-8 mRNA levels were elevated at the end of hour 1 (P=.009) with respect to the control group, but not thereafter. Interstitial changes were minimal. IL-8 mRNA levels during reperfusion were similar to those observed during ischemia, with a slight increase at the end of hour 2. There were no significant differences between hours 1, 2, and 3. Polymorphonuclear neutrophil recruitment occurred at the beginning of reperfusion (P=.014), but no significant differences were observed at hours 2 or 3. Progressive thickening of alveolar septa and edema was documented. Changes in IL-8 mRNA expression during ischemia precede interstitial infiltration by polymorphonuclear neutrophils during reperfusion, suggesting that the 2 processes are related. Quantification of IL-8 mRNA expression could facilitate early diagnosis of graft dysfunction.

Evaluation of accuracy of clinical diagnosis of TB by annual autopsy report

To investigate the accuracy of clinical diagnosis of TB in Japan in recent years and to compare them with previous studies. Data (sex, age, clinical diagnosis, pathological diagnosis as cause of death) on deceased cases clinically or pathologically diagnosed ante mortem as having tuberculosis was collected from annual reports of the pathological autopsy cases in 1984, 1989, 1994, and 1999-2004. Information on TB death from population statistics in those 9 years also was collected and compared with data of autopsied cases. Autopsy rate in these years was stably around 10 %. Comparison of gender ratio and mean age between the two surveys showed similar numbers. During 1999-2004, 1725 death cases were diagnosed as TB clinically or pathologically. Number of pathologically proven pulmonary TB cases was 429 and that of miliary TB was 283. 55.7% of pulmonary tuberculosis and only 21.9% of miliary tuberculosis were correctly diagnosed before death. Out of 156 cases clinically diagnosed as non-TB diseases but proven as TB pathologically, 30.8% of clinical diagnosis was pneumonia and/or bronchitis, followed by diagnoses of interstitial pneumonia, respiratory failure, pneumoconiosis and lung cancer. However, the main clinical diagnoses of 175 miss-diagnosed miliary TB cases were diseases other than pulmonary diseases such as renal failure, malignant diseases and sepsis. In order to reduce undiagnosed pulmonary TB cases and to prevent nosocomial TB infection, differential diagnosis among pneumonia and/or bronchitis cases should be done. In case of miliary TB, not only pneumonia but also diseases other than pulmonary diseases such as renal failure, malignant diseases and sepsis should be included in the list differential diagnosis.

Severe interstitial pneumonia induced by paclitaxel in a patient with adenocarcinoma of the lung.

A 71-year-old Japanese man with adenocarcinoma of the lung developed interstitial pneumonia after treatment with paclitaxel. The patient had acute chills and fever on the fourth day after the second exposure to paclitaxel, rapidly got worse despite empiric therapies, and developed prolonged respiratory failure requiring mechanical ventilation. Four months later, he died of respiratory failure due to progression of both interstitial pneumonia and lung cancer. This is the first case developing fatal paclitaxel-induced pulmonary toxicity to date. Interstitial pneumonia should be considered one of the possible life-threatening complications during treatment with paclitaxel.

Identification of a novel autoantibody reactive with 155 and 140 kDa nuclear proteins in patients with dermatomyositis: an association with malignancy

Myositis-specific autoantibodies (MSAs) are a useful tool in diagnosis, defining clinical subsets and predicting prognosis of dermatomyositis (DM) and polymyositis (PM). In this study, we identified a novel MSA reactive with 155 and 140 kDa nuclear proteins [anti-155/140 antibody (Ab)] and determined the clinical feature of DM patients positive for this autoantibody (autoAb). Sera from 52 Japanese patients with DM, 9 with PM, 48 with systemic lupus erythematosus (SLE), 126 with systemic sclerosis and 18 with idiopathic interstitial pneumonia were examined by immunoprecipitation assays. Positive sera were further characterized by immunodepletion and immunofluorescence staining. Seven of the 52 (13%) Japanese patients with DM immunoprecipitated 155 and 140 kDa proteins from 35S-labelled K562 leukaemia cell extract. No patients with SLE, systemic sclerosis or idiopathic interstitial pneumonia as well as healthy controls were positive for this autoAb. Patients with anti-155/140 Ab developed heliotrope rash, Gottron's papules or sign and flagellate erythema significantly more frequently than those negative. Notably, internal malignancy was found at significantly higher frequency in those positive than those negative (71 vs 11%; P < 0.005). In contrast, none of these patients positive for this autoAb had interstitial lung disease. This novel MSA is associated with cancer-associated DM and may serve as a diagnostic serological marker for this specific subset.

The proportion of general practitioner referrals to a hospital Respiratory Medicine clinic suitable to be seen in a GPwSI Respiratory Clinic

The purpose of this study was to examine the proportion of general practitioner (GP) referrals to a hospital Respiratory Medicine clinic which might be suitable for a General Practitioner with a Special Interest (GPwSI) Respiratory Clinic. All GP referral letters to the Respiratory Medicine Department of a teaching hospital, apart from urgent cancer referrals, were identified from two two-week periods. All patient and practice identifications were removed. Two GPs and one Consultant Respiratory Physician assessed each of the anonymised referral letters to determine the patient's suitability to be seen in a GPwSI Respiratory Clinic, assuming such a clinic had a predetermined range of investigative facilities. Out of 96 referrals covering a wide range of respiratory conditions apart from lung cancer, 22 (23%) were considered by all assessors to be suitable for a GPwSI clinic, and there was full agreement that 40 referrals (42%) were unsuitable. The other 34 referrals (35%) had varying degrees of agreement on suitability. The largest groups of patient referrals considered suitable for a GPwSI clinic were those with chronic obstructive pulmonary disease (COPD) or cough as the main presenting clinical problem. The commonest groups considered unsuitable were referrals of patients with an abnormal chest radiograph, haemoptysis, or possible interstitial lung disease. This small study has shown that at least a fifth of GP referrals to a hospital Respiratory Medicine clinic could be seen in a suitably resourced GPwSI clinic, with consequent reductions in hospital outpatient waiting lists and improved accessibility for patients. This finding will be of interest to potential commissioners of GPwSI services especially with the advent of Practice-based Commissioning.