Pirfenidone and Nintedanib in idiopathic pulmonary fibrosis: Real-life experience in an Italian referral centre.

BACKGROUND: Idiopathic pulmonary fibrosis has a median survival time after diagnosis of 2-5 years. The main goal of treating IPF is to stabilize or reduce the rate of disease progression. Nintedanib and Pirfenidone have been a breakthrough in the management of IPF. Here we evaluated the effectiveness of Pirfenidone and Nintedanib in a population of IPF patients diagnosed in the last 12 months at Florence ILD Referral Centre. METHODS: In the last 12 months, 82 IPF patients (66 male, mean age 78.3±23.8 years) were diagnosed and started antifibrotic therapy with Pirfenidone or Nintedanib. Their clinical and functional details were analyzed retrospectively at time 0 and after 6 and 12 months of therapy. RESULTS: The median age of the patients treated with Nintedanib was higher than that of the Pirfenidone group (p<0.0001). The most common symptoms at disease onset were exertional dyspnoea and dry cough with no differences between the two groups (p<0.05). All IPF patients manifested bibasal crackles at the time of diagnosis. No significant differences in FVC, FEV1, TLC and DLCO were found at time 0 or after 6 months between patients treated with Pirfenidone and Nintedanib (p>0.05). After 1 year, lung function test parameters of patients treated with Pirfenidone had remained stable from baseline. DISCUSSION: This study emphasizes that both antifibrotic drugs appeared to be a good therapeutic choice in terms of functional stabilization, also in older patients.

Gas exchange and breathing pattern in women with postmenopausal bone fragility.

BACKGROUND: Little is known about the relationship between bone fragility and respiratory function. We hypothesized that women with osteoporosis or osteopenia, without cardio-pulmonary disease, have perturbations in the pattern of breathing and gas exchange. METHODS: In 44 women with bone fragility (BF, T score: < -1), and 20 anthropomorphically-matched control women (T score > -1) we compared pulmonary function tests, central respiratory drive (mouth occlusion pressure or P 0.1), pattern of breathing using optoelectronic plethysmograph and arterial blood gases at rest. RESULTS: Static pulmonary function was similar in BF subjects and controls. However, the arterial blood gas measurements differed significantly. The arterial pH was significantly higher in BF subjects than in controls (P < 0.001). The partial pressure of carbon dioxide (PaCO2) and oxygen (PaO2) in arterial blood were significantly lower in BF subjects than controls (P < 0.001 and P = 0.009, respectively). The BF subjects had a shorter inspiratory fraction compared with controls (P = 0.036). Moreover, T-scores were significantly inversely correlated with the alveolar-arterial gradient of oxygen (r = -0.5; P = 0.0003) and the arterial pH (r = -0.4; P = 0.002), and positively correlated with arterial PaO2 (r = 0.3; P = 0.01) and PaCO2 (r = 0.4; P = 0.002) among all subjects. CONCLUSION: In the absence of known cardio-pulmonary disease, BF is associated with statistically significant perturbations in gas exchange and alterations in the pattern of breathing including shortening of the inspiratory time.

Is incidentally detected pulmonary embolism in cancer patients less severe? A case-control study.

Incidental pulmonary embolism (PE) in cancer patients is usually thought to be of mild degree. We investigated the severity of PE and evaluated the potential of raising the suspicion of PE in such patients. The computed tomography (CT) extent of PE was evaluated in 19 consecutive unsuspected and 19 randomly selected symptomatic patients. A clinical pattern useful for suspecting PE was also searched. On CT, number of embolized vessels, location of emboli, and simple instrumental findings were not different in the two groups. PE is not less severe in unsuspected cancer patients; moreover, PE may be clinically suspected in such patients.

Cough. 3: chronic cough and gastro-oesophageal reflux.

The pathogenesis and clinical features of gastro-oesophageal reflux related cough are complex and the diagnostic tests available are of limited reliability. Treatment needs to be tailored to the specific needs of individual patients and other possible causes of chronic cough should be investigated. Treatment should only be considered to have failed when cough persists after administration of proton pump inhibitors at an adequate dosage for a sufficient length of time.

Diagnostic value of gas exchange tests in patients with clinical suspicion of pulmonary embolism.

OBJECTIVE: To assess the value of parameters derived from arterial blood gas tests in the diagnosis of pulmonary embolism. METHOD: We measured alveolar-arterial partial pressure of oxygen [P(A-a)O2] gradient, PaO2 and arterial partial pressure of carbon diaxide (PaCO2) in 773 consecutive patients with suspected pulmonary embolism who were enrolled in the Prospective Investigative Study of Acute Pulmonary Embolism. DIAGNOSIS: The study design required pulmonary angiography in all patients with abnormal perfusion scans. RESULTS: Of 773 scans, 270 were classified as normal/near-normal and 503 as abnormal. Pulmonary embolism was diagnosed by pulmonary angiography in 312 of 503 patients with abnormal scans. Of 312 patients with pulmonary embolism, 12, 14 and 35% had normal P(A-a)O2, PaO2 and PaCO2, respectively. Of 191 patients with abnormal scans and negative angiograms, 11, 13 and 55% had normal P(A-a)O2, PaO2 and PaCO2, respectively. The proportions of patients with normal/near-normal scans who had normal P(A-a)O2, PaO2 and PaCO2 were 20, 25 and 37%, respectively. No differences were observed in the mean values of arterial blood gas data between patients with pulmonary embolism and those who had abnormal scans and negative angiograms. Among the 773 patients with suspected pulmonary embolism, 364 (47%) had prior cardiopulmonary disease. Pulmonary embolism was diagnosed in 151 (41%) of 364 patients with prior cardiopulmonary disease, and in 161 (39%) of 409 patients without prior cardiopulmonary disease. Among patients with pulmonary embolism, there was no difference in arterial blood gas data between patients with and those without prior CPD. CONCLUSION: These data indicate that arterial blood gas tests are of limited value in the diagnostic work-up of pulmonary embolism if they are not interpreted in conjunction with clinical and other laboratory tests.

Resection of single brain metastasis in non-small-cell lung cancer: prognostic factors.

Combined resection of primary non-small-cell lung cancer and single brain metastasis is reportedly superior to other treatments in prolonging survival and disease-free interval. To identify prognostic factors that influenced survival we reviewed clinical records and follow-up data of 52 consecutive patients with non-small-cell lung cancer and single brain metastasis who had been evaluated for combined lung and brain operation: 19 had synchronous and 33 metachronous non-small-cell lung cancer and single brain metastasis. Seven patients were excluded from combined operation because of either early brain relapse after craniotomy or single brain metastasis localization in deep brain structures. Forty-one of the 45 patients who underwent combined operation had complete remission of neurologic symptoms. Actuarial 5-year survival from the second surgical intervention was 16% (median 19 months, range 1 to 104 months). N0 status and lobectomy were the only variables associated with longer survival. Actuarial 5-year survivals in patients with synchronous and metachronous presentation were 6.6% and 19%, respectively. In patients with metachronous presentation the length of survival was significantly associated with N0 status, lobectomy, and interval between lung and brain operation equal to or longer than 14.5 months. The subset of patients with N0 status and interval between operations longer than 14.5 months had a 61% 5-year survival. None of the patients with N1-2 disease and shorter interval between operations was alive at 20 months. These data indicate that prognostic factors may help to identify subsets of patients with markedly different outcomes after combined lung and brain operation.

Pulmonary retention of iodobenzyl-propanediamine in humans. Effect of cigarette smoking.

N,N,N'-trimethyl-N'-(2-hydroxy-3-methyl-5-iodobenzyl)-1,3-propanediamine (HIPDM), a synthetic basic compound with high affinity for lung tissue of various animal species, was labeled with 123I and injected into normal smokers (n = 9) and into asymptomatic smokers (n = 9). Time/activity curves were recorded for 90 min by gamma camera. HIPDM lung clearance was described by two exponential components. In smokers, the mean time of the first component, 10 +/- 1.4 min (mean +/- SEM), did not significantly differ from that of nonsmokers (9.7 +/- 0.9 min), whereas the mean time of the second component (12.9 +/- 0.6 h) was longer than that of nonsmokers (6.7 +/- 0.2 h). The intercept to the ordinate of the second exponential component was significantly higher in smokers (90.3 +/- 1.5%) than in nonsmokers (80.7 +/- 1.9%). Control studies in rabbits showed that, 2 min after intravenous injection, 95% of HIPDM is taken up by the lung; time/activity curves were similar to those obtained in humans. The longer pulmonary persistence of HIPDM in smokers may reflect an increased number of cellular binding sites or may be the expression of hindered HIPDM biotransformation. The rabbit can be used as a model to further investigate HIPDM kinetics in relation to lung dysfunction.

Fatal peripheral airway cystic disease in a young woman.

Diffuse cystic transformation of both lungs was rapidly fatal in a 33-year-old woman. This disorder, a rare congenital condition in infants, has apparently not been described in adulthood.

The radiologic distinction of cardiogenic and noncardiogenic edema.

Improvement in the ability to determine the specific cause of any given case of pulmonary edema would lead to more rapid and definitive treatment. "Wedge" pressures and measurements of cardiac output derived from Swan-Ganz catheterization assist in making this determination, but the procedure is invasive, expensive, associated with complications, and not infrequently inaccurate. A plain chest film is, however, almost invariably available in all patients with pulmonary edema, and as shown in this study, the cause of the edema can be determined with a high degree of accuracy by careful attention to certain radiographic features. An independent two-observer study was performed on 216 chest radiographs of 61 patients with cardiac disease, 30 with renal failure or overhydration, and 28 with capillary permeability edema. Three principal and seven ancillary features have been identified, all of which are statistically significant and permit the cause of the edema to be determined correctly in a high percentage of cases. The three principal features are distribution of pulmonary flow, distribution of pulmonary edema, and the width of the vascular pedicle. The ancillary features are pulmonary blood volume, peribronchial cuffing, septal lines, pleural effusions, air bronchograms, lung volume, and cardiac size. Differing constellations of these features occur, each of which is characteristic of a specific type of edema. Overall accuracy of diagnosis in this study ranged from 86% to 89%. The highest accuracy was obtained in distinguishing capillary permeability edema from all other varieties (91%), and the lowest in distinguishing chronic cardiac failure from renal failure (81%).

Surgical treatment of primary lung cancer and solitary brain metastasis.

Twenty patients with carcinoma of the lung and a brain metastasis have undergone combined lung and brain surgery, which was synchronous in five. There were no operative deaths. Survival from the first surgical intervention was less than one year (3-10 months) in four patients (20%), one to two years in four (20%) and more than two years (26-66 months) in five patients (25%). Seven patients (35%) are alive and well after an average period of three years and three months (15-66 months). Actuarial survival at five years is 33.6%. All patients had severe neurological symptoms and 18 (90%) had a complete remission. Our experience and data reported in the literature point to the effectiveness of combined lung and brain surgery in prolonging symptom free survival in patients with lung cancer and solitary brain metastasis.